Synthesis of crystalline polymers from cyclic diolides

ABSTRACT

Biodegradable polymers with advantageous physical and chemical properties are described, as well as methods for making such polymers. In one embodiment, a new chemical synthesis route to technologically important biodegradable poly(3-hydroxybutyrate) (P3HB) with high isotacticity and molecular weight required for a practical use is described. The new route can utilize racemic eight-membered cyclic diolide (rac-DL), meso-DL, or a rac-DL and meso-DL mixture, derived from bio-sourced dimethyl succinate, and enantiomeric (R,R)-DL and (S,S)-DL, optically resolved by metal-based catalysts. With a stereoselective racemic molecular catalyst, the ROP of rac-DL under ambient conditions produces rapidly P3HB with essentially perfect isotacticity ([mm]&gt;99%), high crystallinity and melting temperature (T m =171° C.), as well as high molecular weight and low dispersity (M n =1.54×10 5  g/mol, Ð=1.01).

RELATED APPLICATIONS

This application claims priority under 35 U.S.C. § 119(e) to U.S.Provisional Patent Application Nos. 62/616,277 filed Jan. 11, 2018, and62/671,069 filed May 14, 2018, which are incorporated herein byreference.

GOVERNMENT SUPPORT

This invention was made with government support under Grant No. 1664915awarded by the National Science Foundation. The government has certainrights in the invention.

BACKGROUND OF THE INVENTION

Naturally produced poly(hydroxyalkanoate)s (PHAs) are a commerciallyimportant class of biodegradable/biocompatible aliphatic polyesters. Themost extensively studied PHA, poly(3-hydroxybutyrate) (P3HB), isconsidered an attractive biodegradable alternative to petroleum-basedplastics. P3HB is an attractive alternative to petroleum-based plasticsdue to its stereoregularity and properties resulting therefrom. However,high production costs and limited production volumes of naturallyproduced PHAs, including P3HB, currently renders their commercial useimpractical.

In the context of creating a synthetic equivalent of naturally producedP3HB, both stereoregularity, more specifically high isotacticity, andhigh molecular weight are typically required for practical use. Currentroutes to synthetic P3HB include the ring opening polymerization (ROP)of f|-butyrolactone (β-BL) via alkyl aluminoxanes, Zn, Co, Cr,Lanthanide, and Y initiator/catalyst complexes. Commercially viable ROPof β-BL in these processes has required the use of the racemic monomer,rac-β-BL. Unfortunately, these initiator/catalyst complexes do not yieldP3HB with the desired stereoregularity and desired properties resultingtherefrom nor the high molecular weight necessary for a syntheticequivalent of naturally produced P3HB to be commercially viable.

Accordingly, there is a need for a new synthetic route to produce highlystereoregular P3HB of high molecular weight. There is also a need for anew initiator/catalyst complex for use in the production of the highlystereoregular P3HB of high molecular weight.

SUMMARY

The invention provides technologically important biodegradable polymerswith physical and chemical properties required for practical use. Theinvention also provides methods for making such polymers. Accordingly,the invention provides a highly isotactic polymer comprising Formula I:

wherein:

n is about 10 to about 10,000;

R is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, or aryl; andFormula I comprises at least 95% isotactic triads with respect to thestereocenters of substituents R on the polymer chain, wherein the atleast 95% isotactic triads (mm) have consecutive (R) stereochemicalconfigurations or consecutive (S) stereochemical configurations.

In one embodiment, the polymer comprises at least 99% isotactic triadswith respect to the stereocenters of substituents R on polymer chain.

In various embodiments, the molecular weight M_(n) is at least about 100kDa.

In various embodiments, the polymer has a melting temperature, T_(m), ofat least 170° C.

The invention also provides a composition comprising polymers describedherein, such as those of Formula I above, wherein the compositioncomprises approximately equal amounts of polymers having isotactictriads of (R) stereochemical configurations and polymers havingisotactic triads of (S) stereochemical configurations.

The dispersity index M_(w)/M_(n) of the polymers described herein can beless than 1.2.

Copolymers described herein can include a polymer described herein incombination with a polyester of lactone monomers.

The invention further provides a copolymer comprising Formula II:

wherein:

x is about 1 to about 100;

y is about 1 to about 100;

n is about 10 to about 5,000;

each R¹ is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, oraryl;

each R² is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, oraryl;

the x block of Formula II comprises at least 95% isotactic triads withrespect to the stereocenters of substituents R¹ on the polymer chain,wherein the at least 95% isotactic triads (mm) have consecutive (R)stereochemical configurations or consecutive (S) stereochemicalconfigurations; and

the y block of Formula II comprises at least 95% isotactic triads withrespect to the stereocenters of substituents R² on the polymer chain,wherein the at least 95% isotactic triads (mm) have consecutive (R)stereochemical configurations or consecutive (S) stereochemicalconfigurations;

wherein the polymer of Formula II is an isotactic random copolymer.

The invention yet further provides a copolymer comprising Formula III:

wherein:

x is about 10 to about 5,000;

y is about 10 to about 5,000;

n is 1-50;

each R is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, oraryl;

the x block of Formula III comprises at least 95% isotactic triads withrespect to the stereocenters of substituents R on the polymer chain,wherein the at least 95% isotactic triads (mm) have consecutive (R)stereochemical configurations or consecutive (S) stereochemicalconfigurations; and

the y block of Formula III comprises consecutive R groups having (R) and(S) configurations, consecutive R groups having (S) and (R)configurations, or consecutive R groups having stereochemicalconfigurations the opposite of the main stereochemical configuration ofthe x block;

wherein the polymer of Formula III is an isotactic-b-syndiotacticstereodiblock or stereotapered copolymer.

The invention additionally provides a copolymer comprising Formula IV:

wherein:

x is about 1 to about 100;

y is about 1 to about 100;

k is about 1 to 16;

n is 10 to about 5,000;

R is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, or aryl; and

the x block of Formula IV comprises at least 95% isotactic triads withrespect to the stereocenters of substituents R on the polymer chain,wherein the at least 95% isotactic triads (mm) have consecutive (R)stereochemical configurations or consecutive (S) stereochemicalconfigurations.

The invention also provides a metal complex of Formula X:

wherein:

M is Sc, Y, or a lanthanide(III) metal;

Ligand is —OR^(x), —NR^(x) ₂, or —N(SiR^(y) ₃)₂, wherein R^(x) is alkyl,and each R^(y) is H or alkyl, wherein at least two R^(y) groups arealkyl;

R^(a) is H, alkyl, or phenyl; and

R^(b) and R^(c) are H, alkyl, or phenyl; or

R^(b) and R^(c) together with the carbon atoms to which they areattached form a 5, 6, 7, or 8 membered cycloalkyl group.

In one embodiment, the metal complex is the complex 4d:

The invention also provides a method for preparing an isotactic orsyndiotactic polymer of Formula I:

wherein:

n is about 10 to about 10,000; and

R is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, or aryl;

the method comprising contacting one or more monomers, an effectiveamount of a metal complex, and an alcohol initiator to initiate a ringopening polymerization reaction;

wherein:

the monomer is a monomer of Formula V:

wherein R is as defined for Formula I; and

the metal complex is a metal complex of Formula X, for example, themetal complex 4d; to thereby form the isotactic or syndiotactic polymerof Formula I.

In one embodiment, Formula I comprises at least 95% isotactic triadswith respect to the stereocenters of substituents R on the polymerchain, wherein the at least 95% isotactic triads (mm) have consecutive(R) stereochemical configurations or consecutive (S) stereochemicalconfigurations.

In another embodiment, the monomer of Formula V is a racemic mixture,the metal complex of Formula X is a racemic mixture, and the polymers ofFormula I formed are a mixture of highly isotactic (R) polymers andhighly isotactic (S) polymers.

In further embodiments, the polymer of Formula I has a molecular weightM_(n) of at least 40 kDa, a dispersity index of less than 1.2, and amelting temperature, T_(m), of at least 171° C.

In additional embodiments, the monomer of Formula V is a mesodiastereomer, and the polymers of Formula I formed are highlysyndiotactic polymers wherein probability of racemic linkages betweenmonomers, P_(r), is greater than 0.94 and the melting temperature,T_(m), of the polymers formed is greater than 174° C.

The invention also provides a method for preparing a polymer of FormulaII:

wherein:

x is about 1 to about 100;

y is about 1 to about 100;

n is about 10 to about 5,000;

each R¹ is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, oraryl;

each R² is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, oraryl;

the method comprising contacting two or more monomers, an effectiveamount of a metal complex, and an alcohol initiator to initiate a ringopening polymerization reaction;

wherein:

the two or more monomers are monomers of Formula V-A and V-B:

wherein R¹ and R² are as defined for Formula II; and

the metal complex is a metal complex of Formula X, for example, themetal complex 4d; to thereby form a isotactic, syndiotactic, orisotactic-b-syndiotactic stereodiblock or stereotapered polymers polymerof Formula II.

In one embodiment, the monomers of Formulas V-A and V-B comprise amixture of meso and racemic diastereomers and the polymers formed areisotactic-b-syndiotactic stereodiblock or stereotapered polymers.

In another embodiment, the monomers of Formulas V-A and V-B comprise amixture of racemic monomers wherein R¹ of Formula V-A is different thanR² of Formula V-B, and the polymers formed are isotactic randomcopolymers.

In further embodiments, the monomers of Formulas V-A and V-B comprise amixture of meso and racemic diastereomers, and wherein R¹ of Formula V-Ais different than R² of Formula V-B, and the polymers formed areisotactic-b-syndiotactic diblock copolymers or stereotapered copolymers.

The invention yet further provides a method of kinetically resolving aracemic mixture of diolides comprising (R,R)-diolides and (S,S)-diolidesof Formula V:

wherein R is (C₁-C₆)alkyl, (C₁-C₆)alkenyl, (C₁-C₆)alkynyl, benzyl, oraryl;

the method comprising contacting the racemic mixture of diolides ofFormula V with an effective amount of a metal complex of Formula (S,S)—Xor (R,R)—X, such as a yttrium complex of (S,S)-4d or (R,R)-4d:

in the presence of an alcohol initiator;

to initiate a ring opening polymerization reaction of the (R,R)-diolidesby the metal complex of Formula (S,S)—X to provide (S,S)-diolides havingan enantiomeric excess of greater than 99% and a polymer of Formula(R)—I:

wherein n is about 50 to about 10,000, and R is as defined for FormulaV; or

to initiate a ring opening polymerization reaction of the (S,S)-diolidesby the metal complex of Formula (R,R)—X to provide (R,R)-diolides havingan enantiomeric excess of greater than 99% and a polymer of Formula(S)—I:

wherein n is about 50 to about 10,000, and R is as defined for FormulaV.

The highly stereoregular polymers produced as described herein aretechnologically important biodegradable polymers useful in thebiomedical, pharmaceutical, and packaging fields.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings form part of the specification and are includedto further demonstrate certain embodiments or various aspects of theinvention. In some instances, embodiments of the invention can be bestunderstood by referring to the accompanying drawings in combination withthe detailed description presented herein. The description andaccompanying drawings may highlight a certain specific example, or acertain aspect of the invention. However, one skilled in the art willunderstand that portions of the example or aspect may be used incombination with other examples or aspects of the invention.

FIG. 1. Stereomicrostructures (tacticities) of P3HB: a)¹H-NMR spectra(CDCl₃) in the methylene region; b)¹³C-NMR spectra (CDCl₃) in thecarbonyl, methylene, and methyl regions. P3HB produced by: 1)[rac-DL]/[4a]=200/1; 2) [rac-DL]/[4b]/=200/1; 3) [rac-DL]/[4c]=200/1; 4)[rac-DL]/[4d]=200/1; 5) [rac-DL]/[4e]=200/1; and 6) comparative exampleof [rac-β-BL]/[4d]=100/1.

FIG. 2. Degree of control over the molecular weight and dispersity inthe ROP of rac-DL. Plots of M_(n) and Ð values of isotactic P3HBproduced by catalyst 4d at varied [rac-DL]/[4d] ratios. The runs at800/1 and 1200/1 ratios under the same conditions (0.8 mL DCM, 60 min)did not achieve quantitative conversions; thus, the ratios used for theplot were adjusted by their conversions (98% and 74%, respectively).

FIG. 3. Thermal properties of P3HB derived from the ROP of rac-DL: a)[rac-DL]/[4a]=200/1 (ΔH_(f)=40.9 J/g); b) [rac-DL]/[4b]=200/1(ΔH_(f)=47.0 J/g); c) [rac-DL]/[4e]=200/1 (ΔH_(f)=56.5 J/g); d)[rac-DL]/[4d]=200/1 (ΔH_(f)=79.3 J/g); e) [rac-DL]/[4d]=400/1(ΔH_(f)=80.4 J/g); f) (6) [rac-DL]/[4d]=1200/1 (ΔH_(f)=78.6 J/g).Crystallization temperature (T_(c)) and melting-transition temperature(T_(m)) taken from the cooling and second heating scans, respectively.

FIG. 4. Thermal stability of P3HB derived from the ROP of rac-DL: a) TGAand DTG of P3HB produced by catalyst 4a, M_(n)=3.20×10⁴ g/mol, Ð=1.03,[mm]=89%; and b) TGA and DTG of P3HB produced by catalyst 4d,M_(n)=1.19×10⁵ g/mol, Ð=1.03, [mm]>99%.

FIG. 5. DSC curves of poly[(R)-3HB] materials: a) Produced via chemicalROP of rac-DL by (S,S)-[4d]; and b) Commercial naturalpoly[(R)-3-hydroxybutyric acid] purchased from Sigma-Aldrich. T_(c) andT_(m) values taken from the cooling and second heating scans,respectively.

FIG. 6. DSC curves of amorphous, atactic P3HB produced via ROP of β-BLby 4d (top) and perfectly isotactic, highly crystalline P3HB produced by4d with [rac-DL]/[4d]=800/1 (ΔH_(f)=78.1 J/g) (bottom). The cooling andsecond heating rate was 10° C./min.

FIG. 7. TGA and DTG curves of P3HB produced by [rac-DL]/[4d]=200/1(M_(n)=3.74×10⁴ g/mol, Ð=1.07, [mm]>99%).

FIG. 8. DSC curves of enantiomeric P3HB by (R,R)-4d and (S,S)-4d: 1)[rac-DL]/[(R,R)-4d]=400/1 (ΔH_(f)=84.8 J/g); 2)[rac-DL]/[(S,S)-4d]=400/1 (ΔH_(f)=78.9 J/g); 3)[rac-DL]/[(R,R)-4d]=800/1 (ΔH_(f)=87.7 J/g); 4)[rac-DL]/[(S,S)-4d]=800/1 (ΔH_(f)=87.4 J/g); 5)[rac-DL]/[(R,R)-4d]=1600/1 (ΔH_(f)=88.2 J/g); 6)[rac-DL]/[S,S)-4d]=1600/1 (ΔH_(f)=82.5 J/g). Crystallization temperature(T_(c)) and melting-transition temperature (T_(m)) taken from thecooling and second heating scans, respectively.

FIG. 9. MALDI-TOF spectrum of P3HB produced with rac-DL/rac-4d/BnOH(20/1/1, 30 s) and plots of m/z values (y) vs the number of rac-DLrepeat units (x).

DETAILED DESCRIPTION

This invention discloses a new chemical synthesis route totechnologically important biodegradable poly(3-hydroxybutyrate) (P3HB)with high isotacticity and molecular weight required for a practicaluse. The new route disclosed herein utilizes racemic eight-memberedcyclic diolide (rac-DL) derived from bio-sourced dimethyl succinate andenantiomeric (R,R)-DL and (S,S)-DL, optically resolved by metal-basedcatalysts, according to some embodiments. With a stereoselective racemicmolecular catalyst, the ROP of rac-DL under ambient conditions producesrapidly P3HB with perfect isotacticity ([mm]>99%), high crystallinityand melting temperature (T_(m)=171° C.), as well as high molecularweight and low dispersity (M_(n)=1.54×10⁵ g/mol, Ð=1.01). Withenantiomeric catalysts, kinetic resolution polymerizations of rac-DLautomatically stops at 50% conversion and yields enantiopure (R,R)-DLand (S,S)-DL with >99% e.e. and the corresponding poly[(S)-3HB] andpoly[(R)-3HB] with high T_(m)=175° C.

Definitions

The following definitions are included to provide a clear and consistentunderstanding of the specification and claims. As used herein, therecited terms have the following meanings. All other terms and phrasesused in this specification have their ordinary meanings as one of skillin the art would understand. Such ordinary meanings may be obtained byreference to technical dictionaries, such as Hawley's Condensed ChemicalDictionary 14^(th) Edition, by R. J. Lewis, John Wiley & Sons, New York,N.Y., 2001.

References in the specification to “one embodiment”, “an embodiment”,etc., indicate that the embodiment described may include a particularaspect, feature, structure, moiety, or characteristic, but not everyembodiment necessarily includes that aspect, feature, structure, moiety,or characteristic. Moreover, such phrases may, but do not necessarily,refer to the same embodiment referred to in other portions of thespecification. Further, when a particular aspect, feature, structure,moiety, or characteristic is described in connection with an embodiment,it is within the knowledge of one skilled in the art to affect orconnect such aspect, feature, structure, moiety, or characteristic withother embodiments, whether or not explicitly described.

The singular forms “a,” “an,” and “the” include plural reference unlessthe context clearly dictates otherwise. Thus, for example, a referenceto “a compound” includes a plurality of such compounds, so that acompound X includes a plurality of compounds X. It is further noted thatthe claims may be drafted to exclude any optional element. As such, thisstatement is intended to serve as antecedent basis for the use ofexclusive terminology, such as “solely,” “only,” and the like, inconnection with any element described herein, and/or the recitation ofclaim elements or use of “negative” limitations.

The term “and/or” means any one of the items, any combination of theitems, or all of the items with which this term is associated. Thephrases “one or more” and “at least one” are readily understood by oneof skill in the art, particularly when read in context of its usage. Forexample, the phrase can mean one, two, three, four, five, six, ten, 100,or any upper limit approximately 10, 100, or 1000 times higher than arecited lower limit. For example, one or more substituents on a phenylring refers to one to five, or one to four, for example if the phenylring is disubstituted.

As will be understood by the skilled artisan, all numbers, includingthose expressing quantities of ingredients, properties such as molecularweight, reaction conditions, and so forth, are approximations and areunderstood as being optionally modified in all instances by the term“about.” These values can vary depending upon the desired propertiessought to be obtained by those skilled in the art utilizing theteachings of the descriptions herein. It is also understood that suchvalues inherently contain variability necessarily resulting from thestandard deviations found in their respective testing measurements. Whenvalues are expressed as approximations, by use of the antecedent“about,” it will be understood that the particular value without themodifier “about” also forms a further aspect.

The term “about” can refer to a variation of ±5%, ±10%, ±20%, or ±25% ofthe value specified. For example, “about 50” percent can in someembodiments carry a variation from 45 to 55 percent, or as otherwisedefined by a particular claim. For integer ranges, the term “about” caninclude one or two integers greater than and/or less than a recitedinteger at each end of the range. Unless indicated otherwise herein, theterm “about” is intended to include values, e.g., weight percentages,proximate to the recited range that are equivalent in terms of thefunctionality of the individual ingredient, composition, or embodiment.The term about can also modify the end-points of a recited range asdiscussed above in this paragraph.

As will be understood by one skilled in the art, for any and allpurposes, particularly in terms of providing a written description, allranges recited herein also encompass any and all possible sub-ranges andcombinations of sub-ranges thereof, as well as the individual valuesmaking up the range, particularly integer values. It is thereforeunderstood that each unit between two particular units are alsodisclosed. For example, if 10 to 15 is disclosed, then 11, 12, 13, and14 are also disclosed, individually, and as part of a range. A recitedrange (e.g., of weight percentages, carbon groups, or monomeric units)includes each specific value, integer, decimal, or identity within therange. Any listed range can be easily recognized as sufficientlydescribing and enabling the same range being broken down into at leastequal halves, thirds, quarters, fifths, or tenths. As a non-limitingexample, each range discussed herein can be readily broken down into alower third, middle third and upper third, etc. For example, blocks ofthe formulas of polymers described herein that are about 1 to about 100can be about 1 to about 110, about 10 to about 110, about 1 to about 90,about 10 to about 90, about 10 to about 80, about 20 to about 80, about1 to about 50, or about 50 to about 100. Likewise, blocks of theformulas of polymers described herein that are about 10 to about 5,000can be about 10 to about 4,000, about 10 to about 3,000, about 10 toabout 2,000, about 10 to about 1,000, about 10 to about 500, about 10 toabout 50, about 100 to about 5,000, about 100 to about 2,500, about 100to about 1,000, about 100 to about 500, about 50 to about 5,000, orabout 50 to about 1,000.

As will also be understood by one skilled in the art, all language suchas “up to”, “at least”, “greater than”, “less than”, “more than”, “ormore”, and the like, include the number recited and such terms refer toranges that can be subsequently broken down into sub-ranges as discussedabove. In the same manner, all ratios recited herein also include allsub-ratios falling within the broader ratio. Accordingly, specificvalues recited for radicals, substituents, and ranges, are forillustration only; they do not exclude other defined values or othervalues within defined ranges for radicals and substituents. It will befurther understood that the endpoints of each of the ranges aresignificant both in relation to the other endpoint, and independently ofthe other endpoint.

One skilled in the art will also readily recognize that where membersare grouped together in a common manner, such as in a Markush group, theinvention encompasses not only the entire group listed as a whole, buteach member of the group individually and all possible subgroups of themain group. Additionally, for all purposes, the invention encompassesnot only the main group, but also the main group absent one or more ofthe group members. The invention therefore envisages the explicitexclusion of any one or more of members of a recited group. Accordingly,provisos may apply to any of the disclosed categories or embodimentswhereby any one or more of the recited elements, species, orembodiments, may be excluded from such categories or embodiments, forexample, for use in an explicit negative limitation.

The term “contacting” refers to the act of touching, making contact, orof bringing to immediate or close proximity, including at the cellularor molecular level, for example, to bring about a physiologicalreaction, a chemical reaction, or a physical change, e.g., in asolution, in a reaction mixture, in vitro, or in vivo.

The term an “effective amount” refers to an amount effective to bringabout a recited effect, such as an amount necessary to form products ina reaction mixture. Determination of an effective amount is typicallywithin the capacity of persons skilled in the art, especially in lightof the detailed disclosure provided herein. The term “effective amount”is intended to include an amount of a compound or reagent describedherein, or an amount of a combination of compounds or reagents describedherein, e.g., that is effective to form products in a reaction mixture.Thus, an “effective amount” generally means an amount that provides thedesired effect.

The term “alkyl” refers to a branched or unbranched hydrocarbon having,for example, from 1-20 carbon atoms, and often 1-12, 1-10, 1-8, 1-6, or1-4 carbon atoms. Examples include, but are not limited to, methyl,ethyl, 1-propyl, 2-propyl (iso-propyl), 1-butyl, 2-methyl-1-propyl(isobutyl), 2-butyl (sec-butyl), 2-methyl-2-propyl (t-butyl), 1-pentyl,2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl,3-methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl,2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl,3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl,3,3-dimethyl-2-butyl, hexyl, octyl, decyl, dodecyl, and the like. Thealkyl can be unsubstituted or substituted, for example, with asubstituent described below. The alkyl can also be optionally partiallyor fully unsaturated. As such, the recitation of an alkyl group caninclude (when specifically stated) alkenyl or alkynyl groups. The alkylcan be a monovalent hydrocarbon radical, as described and exemplifiedabove, or it can be a divalent hydrocarbon radical (i.e., an alkylene).

The term “aryl” refers to an aromatic hydrocarbon group derived from theremoval of at least one hydrogen atom from a single carbon atom of aparent aromatic ring system. The radical attachment site can be at asaturated or unsaturated carbon atom of the parent ring system. The arylgroup can have from 6 to 20 carbon atoms, for example, about 6 to about10 carbon atoms. The aryl group can have a single ring (e.g., phenyl) ormultiple condensed (fused) rings, wherein at least one ring is aromatic(e.g., naphthyl, dihydrophenanthrenyl, fluorenyl, or anthryl). Typicalaryl groups include, but are not limited to, radicals derived frombenzene, naphthalene, anthracene, biphenyl, and the like. The aryl canbe unsubstituted or optionally substituted, as described for alkylgroups.

The term “substituted” indicates that one or more hydrogen atoms on thegroup indicated in the expression using “substituted” or “optionallysubstituted” is replaced with a “substituent”. The number referred to by‘one or more’ can be apparent from the moiety on which the substituentsreside. For example, one or more can refer to, e.g., 1, 2, 3, 4, 5, or6; in some embodiments 1, 2, or 3; and in other embodiments 1 or 2, andif the substituent is an oxo group, two hydrogen atoms are replace bythe presence of the substituent. The substituent can be one of aselection of indicated groups, or it can be a suitable group recitedbelow or known to those of skill in the art, provided that thesubstituted atom's normal valency is not exceeded, and that thesubstitution results in a stable compound. Suitable substituent groupsinclude, e.g., alkyl, alkenyl, alkynyl, alkoxy, halo, haloalkyl,hydroxy, hydroxyalkyl, aryl, aroyl, (aryl)alkyl (e.g., benzyl orphenylethyl), heteroaryl, heterocycle, cycloalkyl, alkanoyl,alkoxycarbonyl, alkylcarbonyloxy, amino, alkylamino, dialkylamino,trifluoromethyl, trifluoromethoxy, trifluoromethylthio, difluoromethyl,acylamino, nitro, carboxy, carboxyalkyl, keto, thioxo, alkylthio,alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl,heteroarylsulfinyl, heteroarylsulfonyl, heterocyclesulfinyl,heterocyclesulfonyl, phosphate, sulfate, hydroxyl amine, hydroxyl(alkyl)amine, and cyano, as well as the moieties illustrated in theschemes and priority documents of this disclosure, and combinationsthereof. Additionally, suitable substituent groups can be, e.g., —X, —R,—O⁻, —OR, —SR, —S⁻, —NR₂, —NR₃, ═NR, —CX₃, —CN, —OCN, —SCN, —N═C═O,—NCS, —NO, —NO₂, ═N₂, —N₃, —NC(═O)R, —C(═O)R, —C(═O)NRR, —S(═O)₂O⁻,—S(═O)₂OH, —S(═O)₂R, —OS(═O)₂OR, —S(═O)₂NR, —S(═O)R, —OP(═O)(OR)₂,—P(═O)(OR)₂, —OP(═O)(OH)(OR), —P(═O)(OH)(OR), —P(═O)(O⁻)₂, —P(═O)(OH)₂,—C(═O)R, —C(═O)X, —C(S)R, —C(O)OR, —C(O)O⁻, —C(S)OR, —C(O)SR, —C(S)SR,—C(O)NRR, —C(S)NRR, or —C(NR)NRR, where each X is independently ahalogen (“halo”): F, Cl, Br, or I; and each R is independently H, alkyl,aryl, (aryl)alkyl (e.g., benzyl), heteroaryl, (heteroaryl)alkyl,heterocycle, heterocycle(alkyl), or a protecting group. As would bereadily understood by one skilled in the art, when a substituent is keto(═O) or thioxo (═S), or the like, then two hydrogen atoms on thesubstituted atom are replaced. In some embodiments, one or more of thesubstituents above can be excluded from the group of potential valuesfor substituents on the substituted group. The various R groups in theschemes of this disclosure can be one or more of the substituentsrecited above, thus the listing of certain variables for such R groups(including R¹, R², R³, etc.) are representative and not exhaustive, andcan be supplemented with one or more of the substituents above. Forexample, a substituted alkyl can be an aryl-substituted alkyl, forexample, benzyl (—Bn).

The term “alkoxy” refers to the group alkyl-O—, where alkyl is asdefined herein. Examples of alkoxy groups include, but are not limitedto, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy,sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, and the like. Thealkoxy can be unsubstituted or substituted.

The term “alcohol” refers to an at least mono-hydroxy-substitutedalkane. A typical alcohol comprises a (C₁-C₁₂)alkyl moiety substitutedat a hydrogen atom with one or more hydroxyl group. Alcohols includemethanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol,s-butanol, t-butanol, n-pentanol, i-pentanol, hexanol, cyclohexanol,heptanol, octanol, nonanol, decanol, benzyl alcohol, phenylethanol, andthe like. The carbon atom chain in alcohols can be straight, branched,cyclic, or aryl. Alcohols can be mono-hydroxy, di-hydroxy, tri-hydroxy,and the like (e.g. saccharides), as would be readily recognized by oneof skill in the art.

The variables and limitations described for one general or specificembodiment for any polymer described herein can also be applied to otherembodiments, for example, other variations of a polymer or formuladescribed herein, and variations of the embodiments provided in theExamples.

Polymers described herein can be polymers of only one type of monomer,or polymers of more than one type of monomer. Accordingly, the polymerscan be random polymers or block copolymers, depending on their method ofsynthesis. In various embodiments, the block copolymers can bestereodiblock copolymers, stereotapered copolymers, stereogradientcopolymers, stereorandom copolymers, or stereo alternating copolymers,for example, as schematically illustrated below, showing actual orapproximate location and/or organization of monomers as a result ofsynthetic preparation.

The term “stereodiblock” as used herein refers to a polymer and/orpolymeric structure comprising an at least two polymeric blocks whereineach block has a stereoregularity unique to the block. This can beunderstood to mean, by way of example, a polymer of repeating unitsAAA-BBB where a first (A) block has either a stereoregular R or Sconfiguration such that essentially all of the A block is of suchconfiguration, and a second (B) block having a stereoregularconfiguration such that essentially all of the B block is the oppositeconfiguration as to the A block.

The term “essentially perfect” as used herein to describe isotacticityrefers to an isotactic polymer wherein no stereo-irregularities can beidentified through standard NMR analysis.

The term “enantiomeric excess” (e.e.) refers to a measurement of thepurity of a chiral substance and can be expressed as a percent of amajor enantiomer present minus the percent of a minor enantiomer presentwherein the enantiomeric excess of a single pure enantiomer such aswhere a chiral substance is all R or all S possesses an enantiomericexcess of 1.0, understood to be 100%, and would be considered opticallypure.

The term “enantiopure” as used herein refers to a compound or sample ofpolymers wherein the chiral centers within the molecule are all of thesame chirality, as determined by NMR analysis or chiral HPLC.

Poly(3-Hydroxybutyrate)s from Racemic and Enantiomeric Cyclic Diolides

Poly(hydroxyalkanoate)s (PHAs) naturally produced by bacteria and otherliving microorganisms from biorenewable resources such as carbohydratesand fats, are an important class of commercially implemented aliphaticpolyesters as biodegradable and/or biocompatible materials forbiomedical, pharmaceutical, and packaging applications. The mostprominent, thus most extensively studied, PHA is poly(3-hydroxybutyrate)(P3HB), in which bacterial poly[(R)-3-hydroxybutyrate], P[(R)-3HB], is aperfectly stereoregular, pure isotactic crystalline thermoplasticmaterial. Thanks to its comparable thermal and mechanical properties tothose of high-performance isotactic polypropylene (it-PP), highlyisotactic P3HB is being considered as an attractive biodegradablealternative to petroleum-based plastics, especially it-PP. However, highcurrent production costs and limited production volumes ofbacterial/microbial PHAs, including P3HB, render them impractical inmany applications in areas such as bio-renewable and biodegradable“green” commodity thermoplastics.

The chemical synthesis via ring-opening polymerization (ROP) of cyclicesters (lactones or lactides), a process typically catalyzed by ametal-based or organic catalyst, offers an alternative route to suchtechnologically important biodegradable aliphatic polyesters. Ringopening polymerization of cyclic esters is often advantageous, thanks toits fast kinetics of the polymerization, scalability of the polymerproduction, and tunability of catalysts and co-monomers. In thiscontext, the ROP of β-butyrolactone (β-BL) has been developed for thechemical synthesis of P3HB (Jedlinski et al. Macromolecules 1998). TheROP of γ-butyrolactone (γ-BL) for the chemical synthesis ofpoly(4-hydroxybutyrate) (P4HB) has also been realized recently (Hong etal. Nat. Chem. 2016).

In the case of the ROP of β-BL, the cost-effective chemical synthesis ofP3HB calls for the use of the racemic monomer, rac-β-BL, rather than themore expensive enantiopure (R)-β-BL, which requires a stereoselectiveROP process to render the formation of isotactic P3HB. However, despiteextensive research efforts since 1960s, the chemical synthesis of P3HBwith isotacticity P_(m) (defined as the probability of meso linkagesbetween monomer units) >0.85 from the ROP of rac-β-BL has provenelusive.

The ROP of rac-β-BL by alkyl aluminoxanes produced a mixture ofiso-enriched P3HB products as a whole (P_(m)=0.62), which werefractionated into atactic and isotactic fractions with the highest P_(m)of 0.85 reported for the acetone-insoluble fraction. A chiral initiatorsystem consisting of ZnEt₂/(R)(−)-3,3-dimethyl-1,2-butanediol alsoyielded a mixture of P3HB products that were fractionated in methanolinto soluble atactic and insoluble (˜25%) isotactic (P_(m)˜0.80)fractions, and a chiral Co(salen)/Et₃Al complex afforded P3HB of lowcrystallinity (no tacticity data). A discrete β-diiminate zinc alkoxideinitiator promoted a controlled ROP of rac-β-BL with high polymerizationrates, but the resulting P3HB is atactic. Cr(III) salophen complexesconverted rac-β-BL into iso-enriched P3HB with P_(m)=0.66, mediumnumber-average molecular weight (M_(n)=4.81×10⁴ g/mol), high dispersity(Ð=5.2), and modest melting-transition temperature (T_(m)=116, 142° C.).Lanthanide (La, Nd) borohydrides supported on silica polymerizedrac-β-BL into P3HB with P_(m)=0.85 and M_(n)=1.15×10⁴ g/mol.

It is worth noting that syndiotactic P3HB materials from being modestlysyndiotactic (P_(r)˜0.70) to highly syndiotactic (P_(r) up to 0.95),have been achieved through the ROP of rac-β-BL using alkyltinoxides anddiscrete yttrium complexes supported by tetradentate, dianionicalkoxy-amino-bis(phenolate) [O⁻,N,O,O⁻] ligands, respectively. This Ycatalyst system has also been utilized for the ROP of functionalβ-lactones such 4-allyloxymethylene-β-propiolactone to afford eitherhighly isotactic (P_(m)=0.93, M_(n)=9.20×10³ g/mol, Ð=1.46) orsyndiotactic (P_(r)=0.91) polymer, depending on the substituents on theligand. In the context of creating a synthetic equivalent of bacterialP3HB, both high isotacticity (P_(m)>0.95) and molecular weight(M_(n)>10⁵ g/mol) are typically required for practical use.

It is informative to point out that the ingenious utilization of acyclic dimer of 1-lactic acid (1-LA) rendered the commercial productionof high-molecular-weight, highly isotactic polylactide (PLA). Theefforts, however, in attempting the chemical synthesis ofhigh-molecular-weight, highly isotactic P3HB have so far been strictlylimited to the use of the cyclic monomer of 3-hydroxybutyric acid (3HB),namely β-BL. However, β-Lactones are known to be carcinogenic(alkylating DNA), and competing ring-opening mechanisms (O-acyl vs.O-alkyl cleavage) were reported for the ROP of such highly strainedmonomers (Arcana et al. Polym. Int. 2000). As the current approach viathe ROP of rac-β-BL has not yet produced P3HB with high molecular weightand high isotacticity (vide supra), we formulated the following threeworking hypotheses to address this long-standing challenge.

First, by analogy of the PLA production, the chemical synthesis of P3HBcould utilize a cyclic dimer of 3HB, namely eight-membered cyclicdiolide (DL, Scheme 1), which is benign and can be readily derived frombio-sourced dimethyl succinate (Seebach et al. Helvetica Chimica Acta1995). Worth noting here is that the enantiopure cyclic trimer of(R)-3HB, obtained in ˜50% yield from the depolymerization of bacterialP[(R)-3HB], was attempted to polymerize back to P3HB but only lowmolecular (M_(n)˜5,000 g/mol) oligomers were obtained (Melchiros et al.Macromolecules 1996). Second, as DL possesses two stereogenic centers,the ROP of its rac and meso diastereomers could lead to variousstereoregular (isotactic, syndiotactic, stereoblock, etc.) P3HBmaterials, depending on the stereoselectivity of the catalyzed ROPprocess. Third, considering significantly increased sterics present inDL relative to β-BL, a higher degree of stereochemical control in thecatalyzed ROP of DL could be expected, thereby potentially generatinghighly stereoregular P3HB materials.

Guided by these hypotheses, we have endeavored the first study of thisproposed new DL route to P3HB and hereby disclose our discovery that thecatalyzed ROP of rac-DL (b in Scheme 1) enabled the highly efficientsynthesis of P3HB with perfect or essentially perfect isotacticity, highcrystallinity and melting temperature, and high molecular weight.

Monomers

Eight-membered-ring cyclic diolides consist of racemic andmeso-diastereomers as shown in Scheme 2 where R is Me (most common), Et,i-Pr and other alkyl groups, as well as alkenyl, alkynyl, aryl, orbenzyl groups. Heteroatom-containing groups such as OR and NR₂ (NR₁R₂)can be used to substitute the R group. Racemic diolides can be opticallyresolved into pure enantiomer, (R,R)-DL and (S,S)-DL during the kineticresolution polymerization. The positions of R group can also be at alphato the carbonyl groups (DL_(α)). Accordingly, each polymer structureshown herein is intended to be modified, in such embodiments, by movingthe R group to the alternate methylene position of the diolide whenmonomers of the “DL_(α)”-type are used in the synthesis of suchpolymers.

wherein R is H, alkyl, such as methyl or ethyl, alkenyl, alkynyl, aryl,or benzyl, each optionally substituted.Polymers

Upon ring-opening polymerization of the above cyclic diolide monomers,P3HB materials, and derivatives thereof (e.g., wherein R is differentthan the natural butyrate moieties), with different stereoregularitiesor tacticities such as isotactic, syndiotactic, atactic, andstereodiblock or multiblock microstructures can be achieved, dependingon whether a racemic, enantiopure, or meso-monomer is used and on thestereoselectivity of the catalyst. Copolymers can also be produced bycopolymerizing between two different cyclic diolides (e.g., R=Me and R═Hor Et) as well as between cyclic diolides with cyclic esters such aslactones and lactides, for example, γ-butyrolactone, δ-valerolactone,ε-caprolactone, lactide, glycolide, and the like. Scheme 3 illustratesgeneral polymer tacticities for a single stereochemistry monomer;polymers prepared from diolides are represented when each R group isduplicated as a result of diolide monomers.

Catalysts

The most effective meta-based catalyst is yttrium complex 4d supportedby a bulky salen ligand (Scheme 4). Other similar complexes 4a-4c(Scheme 4) also work well for the stereoselective ROP of rac-DL. Thecatalyst structure can be substantially modified through thesubstituents on the aromatic ring (typically bulky groups placed at3,5-positions), the backbone linker (cyclohexyl, alkyl, chiral group,etc.), the metal center (Y, Sc, La, Sm and other group 3 and f-blocklanthanides), and the group on the metal (amide, alkoxide, or alkyl).Group 4 (Ti, Zr, Hf) chiral metallocene catalysts can also be used. Thecatalyst can be in a chiral racemic form, an enantiomerically pure form,or an achiral form. In the case of an enantiomerically pure catalyst,kinetic resolution polymerization of racemic diolide can be performed sothat one enantiomer of the racemic monomer pool is selectivelypolymerized first under 50% monomer conversion while the otherenantiomer is optically resolved.

Organic catalysts are those strong organic bases or nucleophiles, suchas triazabicyclodecene (TBD), that can either directly initiate thepolymerization or activate a protic initiator to promote thepolymerization. They can be used alone but are often used in combinationwith a protic initiator. Organic catalysts include strong organic bases,especially polyaminophosphazene superbases such as1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)-phosphoranylidenamino]-2λ⁵,4λ⁵-catenadi(phosphazene) (tBu-P₄); guanidines such as1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), proazaphosphatranes (cyclicazaphosphines), N-heterocyclic carbens, and N-heterocyclic olefins.Anonic versions of organic catalysts/initiators such as urea or thioureaanions can also be used. Chiral organic catalysts can be used to effectkinetic resolution polymerization of rac-DL into chiral polymer andoptically resolved monomer.

Polymerization Processes

The ROP is typically carried out under solvent-free conditions (i.e.,bulk polymerization), or in solution (e.g., in dichloromethane, toluene,et al.), at room temperature in the presence of a catalyst. The catalystcan be used alone but can also be employed in combination with a proticinitiator. Typical initiators include protic compounds such as alcohols(ROH), di-alcohols (HO—R—OH), polyols (compounds containing more thantwo OH groups, or sugars; amines (RNH₂, R₂NH); thiols (RSH), where R isalkyl, aryl, substituted alkyl, or substituted aryl, or deprotonatedmonomers.

Pure rac-DL can be synthesized in a multi-gram scale from bio-sourceddimethyl succinate. At the outset, the ROP of rac-DL was screened withLa[N(SiMe₃)₂]₃ 1 (Scheme 4), a lanthanum complex that has been shown tobe an effective catalyst for the ring-opening (co)polymerization of γ-BLand α-methylene-γ-butyrolactone (MBL). In combination with an alcoholinitiator, the 1/xBnOH (x=2, 3, BnOH=benzyl alcohol) system waseffective for the ROP of rac-DL (20 equiv) in dichloromethane (DCM) atroom temperature (RT), achieving 100% conversion (x=2) in 4 h or 98%(x=3) conversion in 8 h. However, the resulting P3HB exhibited a lowmolecular weight (M_(n)=2.43×10³ g/mol and Ð=1.09 for x=3, Table 1).Furthermore, both ¹H and ¹³C-NMR spectra showed the formation of aniso-biased amorphous material (P_(m)=0.74, x=2; P_(m)=0.70, x=3), whichwas confirmed by observation of only glass-transition temperature(T_(g)) on its differential scanning calorimetry (DSC) curves.

TABLE 1 Results of rac-DL polymerization by La[N(SiMe₃)₂]₃ (1) andbisphenolate yttrium complexes (2a, 2b, and 3) at room temperature ^(a)Catalyst Initiator [rac-DL]/ Time Conv. ^(b) M_(n) ^(c) Ð ^(c) [mm] ^(d)Run (cat) (I) [cat]/[I] (h) (%) (kg/mol) (M_(w)/M_(n)) P_(m) ^(d) (%) 11 BnOH 20/1/3 8 98 2.43 1.09 0.70 59 1 1 BnOH 20/1/2 4 100 n.d. n.d.0.74 63 2  2a BnOH 20/1/1 48 17 n.d. n.d. n.d. n.d. 3  2b BnOH 20/1/1 4844 n.d. n.d. n.d. n.d. 4 3 BnOH 20/1/1 32 76 2.70 1.08 0.76 66 ^(a)Conditions: rac-DL = 0.138 g (0.8 mmol), [rac-DL] = 1.0M, DCM as thesolvent, V_(solvent) = 0.8 mL, the catalyst and initiator amount variedaccording to the [rac-DL]/[cat]/[I] ratio. ^(b) Monomer conversionsmeasured by ¹H NMR spectra of the quenched solution in benzoicacid/chloroform. ^(c) Number-average molecular weights (M_(n)) anddispersity indices (Ð = M_(w)/M_(n)) determined by GPC carried out at40° C. and a flow rate of 0.8 mL/min, with chloroform as the eluent on aViscotek GPCmax VE 2001 instrument equipped with one PLgel 5 μm guardand three PLgel 5 μm mixed-C columns (Polymer Laboratories; linear rangeof MW = 200-2,000,000). The instrument was calibrated with 10 PMMAstandards, and chromatograms were processed with Malvern OmniSECsoftware (version 4.7). ^(d) P_(m) is the probability of meso linkagesbetween HB units, and mm is isotactic triad made up of two adjacent mesodiads, determined by ¹³C{¹H} NMR spectroscopy.

Next, we turned to a ‘privileged class of catalysts’ for the ROP ofcyclic esters, discrete yttrium amido complexes 2 (Scheme 4) (a,R=^(t)Bu; b, R═CMe₂Ph) and alkyl complex 3 (Scheme 4) supported by thetetradentate [O⁻,N,O,O⁻] ligand, which were previously shown to besuperior catalysts for the ROP of γ-BL and MBL as well as highly activecatalysts for the syndiospecific ROP of rac-β-BL. With a highprecatalyst loading of 5 mol % and in combination with 1 equivalent ofBnOH initiator that undergoes instantaneous alcoholysis of the yttriumcomplex to generate the corresponding yttrium alkoxide catalyst, allthree yttrium complexes were active for the ROP of rac-DL, with yttriumalkyl 3 (Scheme 4) being the most active but still rather sluggish (76%conversion after 32 h). Moreover, these catalysts incorporating thetripodal alkoxy-amino-bis(phenolate) ligand afforded onlylow-molecular-weight (M_(n)=2.70×10³ g/mol and Ð=1.08 for catalyst 3;Scheme 4), iso-biased amorphous material (P_(m)=0.76, Table 1). Forcatalysts 2 (Scheme 4), only low conversions were achieved even after 48h (44% by 2a; 17% by 2b), and the P3HB products were not isolated butthe estimated P_(m) values by in situ NMR spectra were similar to thatby catalyst 3 (Scheme 4).

Considering the steric hindrance of rac-DL monomer with theeight-membered-ring framework and the low activity and isoselectivity ofalso sterically encumbered catalysts 1-3 screened, we arrived atsterically more open yttrium racemic salen complexes 4a-e (Scheme 4).Yttrium silylamido complexes 4a-d supported byN,N′-bis(salicylidene)cyclohexanediimine (salcy) ligands and complex 4esupported by the analogous salph ligand were readily synthesized in goodyields (58-83%) according to the procedures established for thesynthesis of known complex 4a and known salen ligands (see Schemes 8-10below). Complex 4a with the classic salen ligand bearing the3,5-di-tert-butyl substituents was first examined for its activity andstereoselectivity towards the ROP of rac-DL. Excitingly, this complex,when combined with 1 equivalent of BnOH initiator, rapidly polymerized20 to 200 equivalents of rac-DL to completion within 20 min at RT.

The molecular weight of the resulting P3HB increased from lowM_(n)=4.77×10³ g/mol (Ð=1.17) to medium M_(n)=3.20×10⁴ g/mol (Ð=1.03)with increasing the [rac-DL]/[4a] ratio from 20/1 to 200/1, and thecalculated initiation efficiency ranged from 74% to 108% (runs 1-4,Table 2) indicating a controlled polymerization. More importantly,complex 4a now yielded isotactic P3HB with P_(m)˜0.91-0.94 and isotactic[mm] triad ˜87-89% based on ¹H and ¹³C-NMR analysis (FIG. 1).Accordingly, the resulting P3HB material became crystalline, exhibitinga T_(m)˜128-146° C., depending on the polymer molecular weight (runs1-4, Table 2).

TABLE 2 Results of rac-DL polymerization by yttrium catalysts 4a-e andBnOH initiator. ^(a) [rac-DL]/ Time Conv. ^(b) M_(n) ^(c) Ð ^(c) [mm]^(e) T_(m) ^(f) Run Catalyst [4] (min) (%) (kg/mol) (M_(w)/M_(n)) I*^(d) (%) P_(m) ^(e) (%) (° C.) 1 4a  20/1 20 100 4.77 1.17 74 0.91 87128/136 2 4a  50/1 20 100 10.9 1.05 80 0.93 87 133/143 3 4a 100/1 20 10023.0 1.04 75 0.94 89 136/145 4 4a 200/1 20 100 32.0 1.03 108 0.93 89 1465 4b 100/1 20 100 25.1 1.03 69 0.95 89 147 6 4b 200/1 20 100 37.3 1.0193 0.95 88 147 7 4c 100/1 20 100 25.7 1.11 63 0.96 93 153/157 8 4c 200/120 100 52.7 1.14 66 0.96 94 156 9 4d 100/1 20 100 20.1 1.07 88 0.99 98161 10 4d 200/1 20 100 37.4 1.07 92 >0.99 >99 164 11 4d 400/1 20 10064.3 1.02 107 >0.99 >99 169 12 4d 800/1 60 98 119 1.03 113 >0.99 >99 17013 4d 1200/1  30 71 154 1.01 95 >0.99 >99 171 14 4e 100/1 20 100 23.71.03 69 0.88 79 121 15 4e 200/1 20 100 43.6 1.24 78 0.89 79 122 ^(a)Conditions: rac-DL = 0.138 g (0.80 mmol), [rac-DL] = 1.0M; DCM as thesolvent, V_(solvent) = 0.8 mL (except for run 13 where V_(solvent) = 0.4mL); room temperature; yttrium catalyst 4 to BnOH initiator ratio fixedat 1/1, and the amount varied according to the [rac-DL]/[4] ratio. ^(b)Conversions of monomers measured by ¹H NMR spectra of the quenchedsolution in benzoic acid/chloroform. ^(c) Weight-average molecularweights (M_(w)), number-average molecular weights (M_(n)), anddispersity indices (Ð = M_(w)/M_(n)) determined by GPC coupled with an18-angle light scattering detector at 40° C. in chloroform. ^(d) Theinitiation efficiency I* = M_(n)(calcd)/M_(n)(exptl), where M_(n)(calcd)= MW(rac-DL) × [rac-DL]/[4] × conv (%) + MW of chain-end groups (BnOH)]= 172.18 × [rac-DL]/[4] × conv (%) + 108.14. ^(e) P_(m) is theprobability of meso linkages between HB units, and mm is isotactic triadmade up of two adjacent meso diads, determined by ¹³C{¹H} NMRspectroscopy. ^(f) T_(m) measured by DSC with the cooling and secondheating rate of 10° C./min for samples produced by 4c-d, 5° C./min forthe samples produced by 4a-b, or 2° C./min for the samples produced by4e.

Replacing the initiator BnOH with i-PrOH lowered the polymerizationactivity by threefold, now requiring 60 min to achieve complete monomer(200 equiv) conversion. Furthermore, the molecular weight(M_(n)=6.07×10⁴ g/mol) of the resulting P3HB was considerably higherthan the theoretical value, thus giving rise to a low initiationefficiency of only 57%, although the P3HB tacticity remained the same.Other alcohols such as Ph₂CHCH₂OH were also found less effective thanBnOH. Therefore, all the subsequent polymerization studies with otheryttrium complexes (4b-e) employed exclusively BnOH as the more effectiveinitiator.

The above exciting results brought about by yttrium salen complex 4aprompted us to investigate possible effects of the salen ligandframework's electronics, sterics, and geometry of the backbone diiminelinker on the rac-DL polymerization activity and stereoselectivity.

In the context of electronic effects, electron withdrawing substituents(e.g., F) introduced to the 5-positions of the salicylidene frameworkwere found to generate a more redox stable and active (salcy)Co(III)catalyst for the copolymerization of epoxide and anhydride monomerpairs. In the present polymerization of rac-DL by (salcy)yttriumcatalyst 4b with the F groups substituted at the 5-positions of thesalcy ligand, only the isotacticity of the resulting P3HB was improvedslightly to now P_(m)=0.95 and T_(m)=147° C. (runs 5 and 6, Table 2), ascompared with the parent tert-butyl substituted catalyst 4a.

Turning to the steric perturbation of the catalyst, the more bulkycumyl-substituted complex 4c produced isotactic P3HB with a noticeablyhigher isotactic [mm] triad of 94% (FIG. 1) and T_(m) of 156° C. (run 8,Table 2), relative to the [mm] of 89% and T_(m) of 146° C. for the P3HBproduced by catalyst 4a under identical conditions (run 4 vs. 8, Table2). These results showed much more pronounced effects of the ligandsterics than electronics on the polymerization stereoselectivity.Therefore, the even more bulky trityl (Ph₃C) groups were substituted atthe 3-positions of the salcy ligand framework to generate catalystracemic 4d. Remarkably, catalyst 4d produced essentially stereo-perfect,pure isotactic P3HB with P_(m)>0.99 and [mm]>99% (run 10, Table 2),while maintaining high polymerization activity (100% monomer conversionin 20 min). Consistent with this NMR-derived stereo-microstructure (FIG.1), the resulting crystalline isotactic P3HB exhibited a high T_(m) of164° C.

Lastly, to probe the possible effects of the geometry of the backbonediimine linker, we examined the performance of the salph-based complex4e for the rac-DL polymerization and found that this catalyst affordedP3HB with a considerably lower isotacticity (P_(m)˜0.88-0.89, [mm]=79%,runs 14 and 15), as compared with the salcy-based analogue complex 4aunder identical conditions (P_(m)˜0.93-0.94, [mm]=89%, runs 3 and 4). Itis worth noting here that the high stereoselectivity of catalysts 4observed for the ROP of rac-DL does not apply to the ROP of rac-β-BL.For example, the ROP of rac-β-BL by the best catalyst of the series, 4d,was not only sluggish (even with a high catalyst loading of 10 mol % thereaction required 8 h to achieve 96% monomer conversion) but alsonon-stereoselective, producing atactic P3HB (FIG. 1, FIG. 6). Theseresults further highlight the importance of the steric interplay andmatching between the catalyst and monomer structures to achieve a highlystereoselective ROP of such racemic lactone and diolide monomers.

Having identified catalyst 4d being the best catalyst of this series, wefurther examined the ability of this catalyst to control the molecularweight so that practically useful high-molecular-weight isotactic P3HBwith M_(n)>10⁵ g/mol could be synthesized. To this end, we varied the[rac-DL]/[4d] feed ratio from 100/1 to 1200/1 and found the molecularweight of the resulting P3HB increased linearly (R²=0.997, FIG. 2) frommedium M_(n)=2.01×10⁴ g/mol (Ð=1.07) to high M_(n)=1.54×10⁵ g/mol(Ð=1.01), while all the Ð values remained low in a narrow range from1.01 to 1.07 (runs 9-13, Table 2). These observations, coupled with thecalculated high initiation efficiencies of >88% for all thepolymerization runs by catalyst 4d, pointed to a well-controlled ROP ofrac-DL.

DSC curves of the isotactic P3HB materials produced by the ROP of rac-DLwith catalysts 4a-4d under identical conditions ([rac-DL]/[4]=200/1,DCM, RT, 20 min, 100% conversion) were compared in FIG. 3. Consistentwith the gradual increase of the isotacticity of P3HB on going from 4ato 4d, the T_(m) value was observed to increase from 146° C. (4a) to147° C. (4b), 156° C. (4c), and 164° C. (4d). Noteworthy also is thesteadily enhanced heat of fusion (ΔH_(f)) from 4a to 4d: 40.9, 47.0,56.5; and 79.3 J/g, which corresponds to an increase in the P3HBcrystallinity from 28% to 32%, 39%, and 54%, relative to the estimatedΔH_(f) ⁰ value (146 J/g) for an infinite crystal of 100% crystallineP3HB. Furthermore, the T_(m) value of the perfectly isotactic P3HBproduced by catalyst 4d depends somewhat on the polymer M_(n). WhenM_(n) was enhanced from 2.01×10⁴ to 3.74×10⁴, 6.43×10⁴, 1.19×10⁵, and1.54×10⁵ g/mol (runs 9-13, Table 2), T_(m) increased accordingly from161 to 164, 169, 170, and 171° C. These are essentially perfectlyisotactic, highly crystalline materials, with high ΔH_(f) values of ˜80J/g (FIG. 3, FIG. 6).

Thermal degradation profiles of the selected isotactic P3HB samplesderived from the ROP of rac-DL by catalysts 4a and racemic 4d wereexamined by thermal gravimetric analysis (TGA). As can be seen from theTGA and derivative thermogravimetry (DTG) curves (FIG. 4), the P3HBproduced by 4a (M_(n)=3.20×10⁴ g/mol, Ð=1.03, [mm]=89%) exhibited adecomposition temperature (T_(d)) (defined by the temperature of 5%weight loss in the TGA curve) of 234° C. and a maximum ratedecomposition temperature (T_(max)) of 274° C. This results in theT_(d)˜90° C. above its T_(m), proving a window for melt processing. AP3HB sample produced by 4d with a similar M_(n) (3.74×10⁴ g/mol) but amuch higher isotacticity of [mm]>99% exhibited a somewhat higher T_(d)of 239° C. and T_(max) of 281° C. (FIG. 7). Keeping the tacticity thesame ([mm]>99%) while increasing the molecular weight to M_(n)=1.19×10⁵g/mol enhanced the T_(d) only slightly to 241° C. (FIG. 4).

The above results demonstrated that the polymerization of rac-DL byrac-4d produced P3HB with essentially perfect isotacticity. However,these exciting results also brought about three important fundamentalquestions: (1) Can enantiomeric catalysts (R,R)-4d and (S,S)-4dkinetically resolve racemic monomer rac-DL; (2) What is thestereocontrol mechanism—enantiomorphic-site control or chain-endcontrol; and (3) What is the isotactic polymer stereomicrostructure—1:1mixture of poly[(R,R)-DL] and poly[(S,S)-DL]), stereoblock ofpoly(rac-DL), or tapered block copolymer poly[(R,R)-DL]-co-[(S,S)-DL].

To address these questions, the corresponding enantiomeric catalysts(R,R)-4d and (S,S)-4d have been successfully synthesized andsubsequently employed to perform kinetic resolution polymerization ofrac-DL with both enantiomeric catalysts, the results of which weresummarized in Table 3. In sharp contrast to the polymerization by rac-4dwith a [rac-DL]/[rac-4d] ratio of 400 or 800 that achieved aquantitative monomer conversion after 20 min, the same polymerization by(R,R)-4d or (S,S)-4d achieved a conversion of ˜50% (runs 1-2 and 4-5,Table 3), after which no further monomer conversion can be achieved,even after extended times (6 h). This is indicative of exclusivecatalyst site selectivity for the ROP of one particular enantiomer ofthe monomer.

TABLE 3 Results of kinetic resolution polymerization of rac-DL byenantiomeric yttrium catalysts (R,R)- and (S,S)-4d and BnOH initiator^(a) [rac-DL]/ Time Conv. M_(n) Ð [mm] T_(m) ^(b) [α]_(D) ²³ e.e. ^(d)Run Catalyst [4d] (min) (%) (kg/mol) (M_(w)/M_(n)) (%) (° C.) (°)^(cx)(%) 1 (R,R)-4d 400/1 20 ~50 43.0 1.07 >99 172 −94.8 >99 2 (R,R)-4d 800/120 ~50 74.8 1.05 >99 172 −94.5 >99 3 (R,R)-4d 1600/1  60 43 118 1.09 >99175 −73.6 80 4 (S,S)-4d 400/1 20 ~50 42.9 1.08 >99 172 +93.7 >99 5(S,S)-4d 800/1 20 ~50 72.1 1.04 >99 172 +94.6 >99 6 (S,S)-4d 1600/1  6044 113 1.07 >99 175 +76.1 86 ^(a) Conditions: rac-DL = 0.241 g (1.40mmol), [rac-DL] = 1.0 M in DCM (1.4 mL); room temperature. See footnotesin Table 2 for other explanations. ^(b) T_(m) measured by DSC with thecooling and second heating rate of 10° C./min. ^(c) Specific rotation([α]_(D) ²³) of the unreacted monomer (DL) in chloroform. ^(d)Enantiomeric excess (e.e.) determined by chiral HPLC.

Characterizations of the ˜50% unreacted, pure monomer exhibitedidentical NMR spectra to that of rac-DL. The specific rotation of theunreacted monomer produced by (R,R)-4d was measured to be from −94.8° to−94.5° (runs 1-2, Table 3), which agrees well with the reported value of(R,R)-DL. The specific rotation of the unreacted monomer by (S,S)-4d wasfrom +93.7 to +94.6 (runs 4-5, Table 3), which is assigned to be(S,S)-DL accordingly. The enantiomeric excess (e.e.) of the unreactedmonomer was determined by chiral HPLC coupled with a Chiralcel OD-Hcolumn and was determined to be >99% e.e. for all the runs withconversion at ˜50% (runs 1-2 and 4-5, Table 3). It is noted here thatthe [rac-DL]/[4d]=1600 runs achieved 43-44% conversion after 60 min(runs 3 and 6); accordingly, the e.e.'s of the unreacted monomer wasonly 80-85%, respectively. Overall, these results indicate that (R,R)-4dexhibits exclusive selectivity for the ROP of (S,S)-DL, while (S,S)-4dpolymerizes (R,R)-DL exclusively. Based on the quantitative e.e.'s(>99%) for the optically resolved, unreacted monomer, thestereoselectivity factor s for both enantiomeric catalysts wascalculated to be >10³. These profound results also indicated anenantiomorphic-site control mechanism for the stereoselective ROPprocess.

This essentially perfect stereoselectivity enabled the synthesis ofenantiomeric poly[(R,R)-DL] and poly[(S,S)-DL] using (S,S)-4d and(R,R)-4d, respectively. The T_(m) values (Table 3, FIG. 8) of theseenantiopure polymers are somewhat higher (by 3-5° C.) than those ofisotactic poly(rac-DL) with similar molecular weights, prepared byrac-4d, and also higher (by 5-7° C.) than that of 1:1 mixture ofpoly[(R,R)-DL] and poly[(S,S)-DL]), indicating no stereocomplexationbetween two enantiomeric P3HB chains. These enantiopure polymers alsoexhibit high ΔH_(f) values in the range of 79˜88 J/g, comparable to thatof natural poly[(R)-3HB]. The highest T_(m) of 175° C. was achieved bythe enantiomeric polymers with M_(n)=113-118 kg/mol (runs 3 and 6, Table3), which, along with the heat of fusion value, is essentially identicalto that of the commercial natural poly[(R)-3HB] (FIG. 5).

To gain further insight into the stereomicrostructure of the highlyisotactic P3HB produced by rac-4d, the polymers produced at differenttimes and [rac-DL]/[rac-4d] ratios were analyzed by matrix-assistedlaser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOFMS). When a low ratio of 20/1 was used with a longer reaction time (20min), the mass spectra showed a pronounced transesterification sidereaction. This side reaction was evidenced by the appearances ofmolecular ion peaks with the spacing between the neighboring peaks beingthat of the half molar mass of the repeat unit, DL (m/z=172.07). Thislow ratio also resulted in a higher dispersity (Ð=1.20) and lowerisotacticity (P_(m)=0.96). Under these conditions, the microstructure ofthe resultant isotactic P3HB is a stereoblock polymer,poly[(R)-3HB]-b-poly[(S)-3HB], resulting from transesterification afterthe reaction reached full conversion (Scheme 5).

Consistent with this reasoning, when the polymerization was quenchedafter 30 s (at which time the full conversion was also achieved), thedispersity of the resulting polymer decreased to Ð=1.09. In addition,its mass spectrum displayed nearly exclusive molecular ion peaks withthe spacing between the neighboring peaks being that of rac-DL. Hereminor peaks were observed with extremely low intensity for the odd 3-HBunits (FIG. 9). These results indicate that the transesterification sidereaction occurred when the reaction reached full conversion and thus canbe essentially shut down by reducing the polymerization time.

In this case, the resulting polymer is predominately a mixture ofpoly[(R)-3HB] and poly[(S)-3HB], with only a trace amount of stereoblockpolymer, poly[(R)-3HB]-b-poly[(S)-3HB]. Obviously, thetransesterification side reaction can be also shut down by reducing thecatalyst amount in feed with the same reaction time, giving the polymerswith very low dispersity indices (Ð=1.01-1.03) at higher[rac-DL]/[rac-4d] feeding ratios. Furthermore, this transesterificationside reaction can be shut down by the use of enantiomeric purecatalysts.

Overall, the polymerization of rac-DL by rac-4d, when stopped at fullconversion (i.e., no transesterification side reactions), produces amixture of poly[(R)-3HB] and poly[(S)-3HB], due to its exclusive(R,R)-4d/(S,S)-DL and (S,S)-4d/(R,R)-DL catalyst/monomer selectivity asdemonstrated by the kinetic resolution results.

In summary, the new approach via the ROP of the bio-sourced rac-DL hassuccessfully addressed the 50⁺-year challenge in the chemical synthesisof bacterial P3HB. This success was enabled by the specifically designedstereoselective molecular catalyst and its steric interplay with themonomer structure, thereby producing the desired P3HB material withperfect isotacticity ([mm]>99%), high crystallinity and meltingtemperature (T_(m)=171° C.), as well as high molecular weight and lowdispersity (M_(n)=154 kg/mol, Ð=1.01). This novel ROP of rac-DL alsoexhibits a high polymerization rate and efficiency. The resulting highlyisotactic P3HB by rac-4d is showed to be the mixture of poly[(R)-3HB]and poly[(S)-3HB] when the polymerization is stopped at full conversion.Thanks to the exclusive (R,R)-4d/(S,S)-DL and (S,S)-4d/(R,R)-DLcatalyst/monomer selectivity, kinetic resolution polymerization ofrac-DL with enantiomeric catalysts automatically ceases at 50%conversion and yields enantiopure (R,R)-DL and (S,S)-DL with >99% e.e.and the corresponding poly[(S)-3HB] and poly[(R)-3HB] with highT_(m)=175° C. and crystallinity, which is essentially identical to thatof the commercial natural poly[(R)-3HB].

The tunability of the catalyst structure allows a rapid entry to P3HBmaterials with various tacticities (thus tunable thermal and mechanicalproperties) and predicted molecular weights with low dispersity indices(vs. a typical Ð value of ˜2.0 for bacterial P3HB). In addition, themolecular catalysts should allow copolymerization of rac-DL with othermonomers to produce 3HB-based copolymers. Altogether, this new ROP of DLrepresents a paradigm shift in the chemical synthesis of P3HB and opensup a plethora of opportunities for discovering new catalysts, materials,and processes in the ROP of rac-DL and other diastereomers of 3HB cyclicdimers or trimers, and so on.

Embodiments of the Invention

In various embodiments, the invention provides a highly isotacticpolymer comprising Formula I:

wherein:

n is about 10 to about 10,000;

R is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, or aryl; and

Formula I comprises at least 95% isotactic triads with respect to thestereocenters of substituents R on the polymer chain, wherein the atleast 95% isotactic triads (mm) have consecutive (R) stereochemicalconfigurations or consecutive (S) stereochemical configurations.

In one embodiment, the polymer comprises at least 99% isotactic triadswith respect to the stereocenters of substituents R on polymer chain. Invarious embodiments, the probability of meso linkages between monomers,P_(m), for the polymer of Formula I is greater than 0.99.

In one embodiment, the molecular weight M_(n) is at least about 20 kDa.In additional embodiments, the molecular weight M_(n) is at least about35 kDa, at least about 50 kDa, at least about 100 kDa, at least about150 kDa, at least about 200 kDa, or at least about 250 kDa. In certainembodiments, the molecular weight is about 1×10³ daltons to about 1×10⁶daltons, about 1×10⁴ daltons to about 5×10⁵ daltons, or about 2×10⁴daltons to about 2×10⁵ daltons.

In various embodiments, the polymer has a melting temperature, T_(m), ofat least 160° C. The polymers typically have a melting temperature,T_(m), of at least 165° C., at least 169° C., at least 170° C., at least171° C., at least 172° C., at least 173° C., or at least 174° C.

In some embodiments, the polymer has a crystallinity of at least about20%, at least about 30%, at least about 40%, or at least about 50%. Incertain embodiments, the polymer has a crystallinity of about 20% toabout 60%, or about 30% to about 55%. In one specific embodiment, thepolymer has a crystallinity of at least about 50% and a heat of fusionΔH_(f) of at least about 72 J/g.

The invention also provides a composition comprising polymers describedherein, such as those of Formula I above, wherein the compositioncomprises approximately equal amounts of polymers having isotactictriads of (R) stereochemical configurations and polymers havingisotactic triads of (S) stereochemical configurations. In certainembodiments, the polymers comprise at about 90% to about 99% isotacticpentads with respect to the carbons having substituent R of the polymerchains.

In one specific embodiment, the polymer of Formula I has a molecularweight M_(n) of at least 40 kDa or at least about 100 kDa, a dispersityindex of less than 1.2, and a melting temperature, T_(m), of at least171° C.

The dispersity index M_(w)/M_(n) of the polymers described herein can beless than about 1.2. In certain embodiments, the dispersity indexM_(w)/M_(n) of the polymers is less than 1.2, less than 1.1, less than1.09, less than 1.08, less than 1.07, less than 1.06, or less than 1.05.In some embodiments, the polymer dispersity is about 1.01 to about 1.1,about 1.01 to about 1.09, about 1.01 to about 1.08.

Copolymers described herein can include a polymer described herein incombination with a polyester of lactone monomers.

The invention further provides a copolymer comprising Formula II:

wherein:

x is about 1 to about 100;

y is about 1 to about 100;

n is about 10 to about 5,000;

each R¹ is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, oraryl; and

each R² is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, oraryl.

The x block of Formula II comprises at least 95% isotactic triads withrespect to the stereocenters of substituents R¹ on the polymer chain,wherein the at least 95% isotactic triads (mm) have consecutive (R)stereochemical configurations or consecutive (S) stereochemicalconfigurations.

The y block of Formula II comprises at least 95% isotactic triads withrespect to the stereocenters of substituents R² on the polymer chain,wherein the at least 95% isotactic triads (mm) have consecutive (R)stereochemical configurations or consecutive (S) stereochemicalconfigurations. Additionally and/or alternatively, the y block ofFormula II comprises consecutive R² groups having (R) and (S)configurations, consecutive R² groups having (S) and (R) configurations,or consecutive R² groups having stereochemical configurations theopposite of the main stereochemical configuration of the x block.

The polymer of Formula II can comprise isotactic random copolymerportions and/or syndiotactic random copolymer portions.

The invention yet further provides a copolymer comprising Formula III:

wherein:

x is about 10 to about 5,000;

y is about 10 to about 5,000;

n is 1-50;

each R is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, oraryl;

the x block of Formula III comprises at least 95% isotactic triads withrespect to the stereocenters of substituents R on the polymer chain,wherein the at least 95% isotactic triads (mm) have consecutive (R)stereochemical configurations or consecutive (S) stereochemicalconfigurations; and

the y block of Formula III comprises consecutive R groups having (R) and(S) configurations, consecutive R groups having (S) and (R)configurations, or consecutive R groups having stereochemicalconfigurations the opposite of the main stereochemical configuration ofthe x block;

wherein the polymer of Formula III is an isotactic-b-syndiotacticstereodiblock or stereotapered copolymer. Also provided are methods ofmaking the polymers of Formula III by selection of the correspondingdiolides and appropriate catalyst. For example, a copolymer comprisingFormula III, such as an isotactic-b-syndiotactic block polymer, can beprepared as shown in Scheme A:

The invention additionally provides a copolymer comprising Formula IV:

wherein:

x is about 1 to about 100;

y is about 1 to about 100;

k is about 1 to 16;

n is 10 to about 5,000; R is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl,(C₁-C₈)alkynyl, benzyl, or aryl; and

the x block of Formula IV comprises at least 95% isotactic triads withrespect to the stereocenters of substituents R on the polymer chain,wherein the at least 95% isotactic triads (mm) have consecutive (R)stereochemical configurations or consecutive (S) stereochemicalconfigurations.

Polymers comprising Formula IV can be made as described herein. Forexample, an isotactic PHA-polylactone random copolymer can be preparedas shown in Scheme B:

The invention also provides a metal complex of Formula X:

wherein:

M is Sc, Y, or a lanthanide(III) metal;

Ligand is —OR^(x), —NR^(x) ₂, or —N(SiR^(y) ₃)₂, wherein R^(x) is alkyl,and each R^(y) is H or alkyl, wherein at least two R^(y) groups arealkyl;

R^(a) is H, alkyl, or phenyl; and

R^(b) and R^(c) are H, alkyl, or phenyl; or

R^(b) and R^(c) together with the carbon atoms to which they areattached form a 5, 6, 7, or 8 membered cycloalkyl group.

In one embodiment, the metal complex is the complex 4d:

The invention also provides a method for preparing an isotactic orsyndiotactic polymer of Formula I:

wherein:

n is about 10 to about 10,000; and

R is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, or aryl;

the method comprising contacting one or more monomers, an effectiveamount of a metal complex, and an alcohol initiator to initiate a ringopening polymerization reaction;

wherein:

the monomer is a monomer of Formula V:

wherein R is as defined for Formula I; and

the metal complex is a metal complex of Formula X, for example, themetal complex 4d; to thereby form the isotactic or syndiotactic polymerof Formula I.

In one embodiment, Formula I comprises at least 95% isotactic triadswith respect to the stereocenters of substituents R on the polymerchain, wherein the at least 95% isotactic triads (mm) have consecutive(R) stereochemical configurations or consecutive (S) stereochemicalconfigurations.

In another embodiment, the monomer of Formula V is a racemic mixture,the metal complex of Formula X is a racemic mixture, and the polymers ofFormula I formed are a mixture of highly isotactic (R) polymers andhighly isotactic (S) polymers.

In further embodiments, the polymer of Formula I has a molecular weightM_(n) of at least 40 kDa, a dispersity index of less than 1.2, and amelting temperature, T_(m), of at least 171° C.

In additional embodiments, the monomer of Formula V is a mesodiastereomer, and the polymers of Formula I formed are highlysyndiotactic polymers wherein probability of racemic linkages betweenmonomers, P_(r), is greater than 0.94 and the melting temperature,T_(m), of the polymers formed is greater than 174° C. In furtherembodiments, method can employ a pair of meso diastereomers to provide apolymer of Formula I.

In one embodiment, a polymer comprising Formula I can be prepared asshown in Scheme C:

to provide a mixture of poly(R)-DL and poly(S)-DL polymers of Formula I.

In another embodiment, a polymer comprising Formula I can be prepared asshown in Scheme D:

to provide a syndiotactic polymer.

The invention also provides a method for preparing a polymer of FormulaII:

wherein:

x is about 1 to about 100;

y is about 1 to about 100;

n is about 10 to about 5,000;

each R¹ is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, oraryl;

each R² is (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, oraryl;

the method comprising contacting two or more monomers, an effectiveamount of a metal complex, and an alcohol initiator to initiate a ringopening polymerization reaction;

wherein:

the two or more monomers are monomers of Formula V-A and V-B:

wherein R¹ and R² are as defined for Formula II; and

the metal complex is a metal complex of Formula X, for example, themetal complex 4d; to thereby form a isotactic, syndiotactic, orisotactic-b-syndiotactic stereodiblock or stereotapered polymers polymerof Formula II.

In one embodiment, the monomers of Formulas V-A and V-B comprise amixture of meso and racemic diastereomers and the polymers formed areisotactic-b-syndiotactic stereodiblock or stereotapered polymers.

In another embodiment, the monomers of Formulas V-A and V-B comprise amixture of racemic monomers wherein R¹ of Formula V-A is different thanR² of Formula V-B, and the polymers formed are isotactic randomcopolymers.

In further embodiments, the monomers of Formulas V-A and V-B comprise amixture of meso and racemic diastereomers, and wherein R¹ of Formula V-Ais different than R² of Formula V-B, and the polymers formed areisotactic-b-syndiotactic diblock copolymers or stereotapered copolymers.

The invention yet further provides a method of kinetically resolving aracemic mixture of diolides comprising (R,R)-diolides and (S,S)-diolidesof Formula V:

wherein R is (C₁-C₆)alkyl, (C₁-C₆)alkenyl, (C₁-C₆)alkynyl, benzyl, oraryl;

the method comprising contacting the racemic mixture of diolides ofFormula V with an effective amount of a metal complex of Formula (S,S)—Xor (R,R)—X, such as a yttrium complex of (S,S)-4d or (R,R)-4d:

in the presence of an alcohol initiator;

to initiate a ring opening polymerization reaction of the (R,R)-diolidesby the metal complex of Formula (S,S)—X to provide (S,S)-diolides havingan enantiomeric excess of greater than 99% and a polymer of Formula(R)—I:

wherein n is about 50 to about 10,000, and R is as defined for FormulaV; or

to initiate a ring opening polymerization reaction of the (S,S)-diolidesby the metal complex of Formula (R,R)—X to provide (R,R)-diolides havingan enantiomeric excess of greater than 99% and a polymer of Formula(S)—I:

wherein n is about 50 to about 10,000, and R is as defined for FormulaV. In one embodiment, the polymer of Formula (R)—I or the polymer ofFormula (S)—I has a molecular weight Mn of at least 40 kDa, a dispersityindex M_(w)/M_(n) of less than 1.09, and a melting temperature T_(m) ofat least 171° C.

The ring-opening polymerizations can be carried out at any suitable andeffective temperature. However, the polymerizations typically proceedrapidly at less than 25° C., or at about room temperature (21-23° C.).Furthermore, the polymerizations can be carried out in any suitable andeffective solvent, such as dichloromethane, THF, dioxolane, or the like.Alternatively, the polymerizations can be carried out without solvent.

The following Examples are intended to illustrate the above inventionand should not be construed as to narrow its scope. One skilled in theart will readily recognize that the Examples suggest many other ways inwhich the invention could be practiced. It should be understood thatnumerous variations and modifications may be made while remaining withinthe scope of the invention.

EXAMPLES

General Materials and Methods.

All syntheses and manipulations of air- and moisture-sensitive chemicalsand materials were carried out in flamed Schlenk-type glassware on adual-manifold Schlenk line, on a high-vacuum line, or in an inert gas(Ar or N₂)-filled glovebox. NMR-scale reactions were conducted inTeflon-valve-sealed J. Young-type NMR tubes. HPLC-grade organic solventswere first sparged extensively with nitrogen during filling 20 L solventreservoirs and then dried by passage through activated alumina (fordichloromethane, DCM) followed by passage through Q-5 supported coppercatalyst (for toluene and hexanes) stainless steel columns. Benzene-d₆was dried over sodium/potassium alloy and filtered, whereas CD₂Cl₂ andCDCl₃ were dried over CaH₂, vacuum-distilled and stored activatedDavison 4 Å molecular sieves. HPLC chromatograms were obtained on anAgilent 1100 series system using a Chiralcel OD-H column withhexanes/isopropanol (80/20) as the eluent at a flow rate of 1.0 mL/min.Optical rotations were measured with an Autopol-III automaticpolarimeter. NMR spectra were recorded on a Varian Inova or BrukerAV-III 400 MHz spectrometer (400 MHz, ¹H; 100 MHz, ¹³C). Chemical shiftsfor ¹H and ¹³C spectra were referenced to internal solvent resonancesand are reported as parts per million relative to SiMe₄. Elementalanalyses were performed by Robertson Microlit Laboratories, Madison,N.J.

Tri[N,N-bis(trimethylsilyl)amide] lanthanum(III) La[N(SiMe₃)₂]₃, yttriumchloride YCl₃, and (trimethylsilyl)methyllithium (SiMe₃)₂CH₂Li solutionin pentane were purchased from Sigma-Aldrich Chemical Co. and used asreceived. 2,2-Diphenylethanol was purchased from Aldrich Chemical Co.,which were purified by sublimation twice. Isopropanol and benzyl alcoholwere purchased from Fisher Scientific Co. and Alfa Aesar Chemical Co.,respectively, which were purified by distillation over CaH₂ and storedover activated Davison 4 Å molecular sieves. Dimethyl succinate, sodiummethoxide and 3-chloroperoxybenzoic acid (mCPBA, 70-75%) were purchasedfrom Fisher Scientific Co. and used as received. Iodomethane waspurchased from Alfa Aesar Chemical Co. and used as received. Thefollowing compounds, ligands, and complexes were prepared according totheir respective literature procedures: Y[N(SiHMe₂)₂]₃(THF)₂, asdescribed by Anwander et al. (J, Chem. Soc. Dalton Trans. 1998,847-858), and Eppinger et al. (Polyhedron 1998, 17, 1195-1201); andyttrium complexes 2 and 3 supported by the tetradentate, dianionicalkoxy-amino-bis(phenolate) [O⁻,N,O,O⁻] ligands, as described by Amgouneet al. (Chem. Eur. J. 2006, 12, 169-179). The monomer, racemiceight-membered cyclic diolide (rac-DL) was prepared according to theliterature route described by Seebach et al. (Helvetica Chimica Acta1995, 78, 1525-1540), and White (J. Org. Chem. 1990, 55, 5938-5940),however the procedures were significantly modified and thus described indetail below; the monomer was purified by sublimation twice prior topolymerization runs.

Polymer Characterizations.

Measurements of polymer absolute weight-average molecular weight(M_(w)), number-average molecular weight (M_(n)), and molecular weightdistributions or dispersity indices (Ð=M_(w)/M_(n)) were performed viagel-permeation chromatography (GPC). The GPC instrument consisted of anAgilent HPLC system equipped with one guard column and two PLgel 5 μmmixed-C gel permeation columns and coupled with a Wyatt DAWN HELEOS IImulti (18)-angle light scattering detector and a Wyatt Optilab TrEX dRIdetector. The analysis was performed at 40° C. using chloroform as theeluent at a flow rate of 1.0 mL/min, using Wyatt ASTRA 7.1.2 molecularweight characterization software. The refractive index increment (dn/dc)of P3HB was determined to be 0.0254±0.0004 mL/g, obtained by batchexperiments using Wyatt Optilab TrEX dRI detector and calculated usingASTRA software. Polymer solutions were prepared in chloroform andinjected into dRI detector by Harvard Apparatus pump 11 at a flow rateof 0.25 mL/min. A series of known concentrations were injected and thechange in refractive index was measured to obtain a plot of change inrefractive index versus change in concentration ranging from 0.4 to 4.0mg/mL. The slope from a linear fitting of the data was the dn/dc of thepolymer.

The isolated low molecular weight samples were analyzed bymatrix-assisted laser desorption/ionization time-of-flight massspectroscopy (MALDI-TOF MS). The experiment was performed onMicroflex-LRF mass spectrometer (Bruker Daltonics, Billerica, Mass.)operated in positive ion, reflector mode using a Nd:YAG laser at 355 nmand 25 kV accelerating voltage. A thin layer of a 1% NaI solution wasfirst deposited on the target plate, followed by 0.6 μL of both sampleand matrix (dithranol in chloroform). External calibration was doneusing a peptide calibration mixture (4 to 6 peptides) on a spot adjacentto the sample. The raw data was processed in the FlexAnalysis software(version 3.4.7, Bruker Daltonics).

Melting transition (T_(m)) and glass transition (T_(g)) temperatureswere measured by differential scanning calorimetry (DSC) on an Auto Q20,TA Instrument. All T_(m) and T_(g) values were obtained from a secondscan after the thermal history was removed from the first scan. Thesecond heating rate was 10° C./min and cooling rate was 10° C./minunless indicated otherwise in the polymerization tables. Decompositiontemperatures (T_(d), defined by the temperature of 5% weight loss) andmaximum rate decomposition temperatures (T_(max)) of the polymers weremeasured by thermal gravimetric analysis (TGA) on a Q50 TGA Analyzer, TAInstrument. Polymer samples were heated from ambient temperatures to700° C. at a heating rate of 10° C./min. Values of T_(max) were obtainedfrom derivative (wt %/° C.) vs. temperature (° C.) plots, while T_(d)and T_(onset) values (initial and end temperatures) were obtained fromwt % vs. temperature (° C.) plots.

The crystallinity of the resulting P3HB was calculated using theequation X_(c) (%)=(ΔH_(f)/ΔH_(f) ⁰)×100, where ΔH_(f) and ΔH_(f) ⁰ isthe heat of fusion (J/g) of the synthesized P3HB and the 100%crystalline P3HB (146 J/g), respectively. Assignments of P3HBtacticities or stereo-microstructures were made through analysis ofpolymer samples by ¹H and ¹³C-NMR analysis, following the establishedliterature assignments and procedures.

Example 1. Synthesis of Racemic Eight-Membered Cyclic Diolide (Rac-DL)

The following illustrates a process for preparing a racemic eightmembered cyclic diolide, rac-DL.

Pure racDL can be synthesizes in a multi-gram scale from bio-sourcesdimethyl succinate as described below.

Typical diolides where prepared by adding a methyl group to structure(i) in Scheme 7 by deprotonation and addition of methyl iodide. As wouldbe readily recognized by one of skill in the art, other diolides where Rof Formula V, V-A, and V-B are (C₁-C₁₈)alkyl, (C₁-C₈)alkenyl,(C₁-C₈)alkynyl, benzyl, or aryl can be likewise prepared by addition ofthe appropriate iodide (or other halide) to deprotonated structure (i).Furthermore, diolides of the “DL_(α)”-type can be obtained commerciallyor by the preparations known in the art.

Dimethyl 2,5-dioxocyclohexane-1,4-dicarboxylate (i)

A solution of sodium methoxide (185 mL, 5.4 M, 1.0 mol) was added todimethyl succinate (73.1 g, 0.5 mol) in one portion, and the mixture washeated under reflux for 24 h. A thick pink-colored precipitate was thenformed and remained throughout the reaction. The methanol was removedusing evaporator, a 2N sulfuric acid solution (500 mL) was added to theresidue, and the mixture was stirred vigorously for 4 h.

The solid was collected by filtration and washed several times withwater. The air-dried product was a pale-buff powder, which wasrecrystallized from 300 mL ethyl acetate. The filtrate was chilled toyield cream to pink-cream colored crystals of dimethyl2,5-dioxocyclohexane-1,4-dicarboxylate (i), 24.5 g (43%); ¹H NMR (400MHz, CDCl₃): δ 12.12 (s, 1H, —CH—), 3.79 (s, 3H, —CO₂CH₃), 3.18 (s, 2H,—CH₂—).

Dimethyl 1,4-dimethyl-2,5-dioxocyclohexane-1,4-dicarboxylate (ii)

To a stirred suspension of K₂CO₃ (41.5 g, 0.3 mol) in 400 mL DMF underN₂ was added i (22.8 g, 0.1 mmol). After 15 min stirring at roomtemperature, MeI (56.8 g, 0.4 mmol) was added dropwise. After 15 h, themixture was concentrated in vacuo, dissolved in 300 mL of H₂O, andextracted with CH₂Cl₂ (120 mL×5). The combined organic layers werewashed with 10% Na₂S₂O₃ solution, dried with anhydrous Na₂SO₄, andevaporated. The residue was purified by column chromatography to yielddimethyl 1,4-dimethyl-2,5-dioxocyclohexane-1,4-dicarboxylate give (ii),20.8 g (81%) as a 2:1 mixture of diastereoisomers. ¹H NMR (400 MHz,CDCl₃), main diastereoisomer: δ 3.72 (s, 6H, MeO); v_(A)=3.15,v_(B)=2.81 (AB, J_(AB)=15.2, 4H, CH₂); 1.44 (s, 6H, Me); minordiastereoisomer: δ 3.74 (s, 6H, MeO); v_(A)=3.44, v_(B)=2.61 (AB,J_(AB)=15.7, 4H, CH₂); 1.41 (s, 6H, Me).

Synthesis of 2,5-dimethylcyclohexane-1,4-dione (iii)

To a stirred suspension of ii (20.5 g, 80 mmol) in 40 mL of conc. H₂SO₄were added 3 mL of methanol and 45 g of crushed ice. After 15 min, themixture was heated to 100° C. for an additional 2 h. The acidic solutionwas cooled to room temperature, neutralized with aq. NaOH (pH 6-7), andextracted with CH₂Cl₂ (150 mL×3). The combined organic layers were driedwith anhydrous Na₂SO₄, and evaporated. The residue was purified bycolumn chromatography to yield racemic 2,5-dimethylcyclohexane-1,4-dione(iii), 10.2 g (91%) at a racemic to meso ratio of about 70:30.

4,8-Dimethyldioxocane-2,6-dione (rac-DL)

To a solution of iii (10.0 g, 71 mmol) in 300 mL of CH₂Cl₂ was addedm-CPBA (52.7 g, 70%, 213 mmol) in one portion. The pale-yellow solutionwas stirred at room temperature in the dark for 48 h. The obtained whitesuspension was diluted with 200 mL of CH₂Cl₂, washed saturated NaHCO₃solution (200 mL×3), which contained 5% Na₂S₂O₃, dried with anhydrousNa₂SO₄, and evaporated. Recrystallization of the residue (10.5 g) fromhexanes/ethyl acetate (5/1) for approximately 3 to 6 times, yielded pureracemic 4,8-Dimethyldioxocane-2,6-dione (rac-DL) 5.1 g. ¹H NMR (400 MHz,CDCl₃): δ 5.35-5.23 (m, 2H, MeCHO—C═O), v_(A)=2.65, v_(B)=2.53, (AB ofABX, J_(AB)=11.4, J_(AX)=9.7, J_(BX)=3.6, 4H, CH₂), 1.44 (d, J=6.4 Hz,6H, Me).

Example 2. Synthesis of Yttrium Complexes 4a-c, and e

The following illustrates a process for preparing a racemic yttriumcomplexes 4a-c.

Synthesis of Salicylaldehydes L^(2a-c)3,5-Bis(tert-butyl)salicylaldehyde L^(2a)

2,4-Di-tert-butylphenol (30.45 g, 0.147 mol), 2,6-lutidine (6.9 mL,0.059 mmol) and 100 mL anhydrous toluene were measured into a side-armround-bottom flask under nitrogen. Tin(IV) chloride (1.72 mL, 14.7 mmol)was added slowly to the reaction flask. The mixture was stirred at roomtemperature for 30 min, and then paraformaldehyde (9.74 g, 0.325 mol)was added. The resulting yellowish solution was heated at 100° C. for 8h, after which time TLC analysis indicated >99% consumption of thephenol. The mixture was allowed to cool to room temperature, and 600 mLwater was added to the flask. The aqueous layer was acidified toapproximately pH=2 with 2N HCl. The aqueous layer was extracted withdiethyl ether, and the combined ether extracts were dried over anhydrousNa₂SO₄. The concentrated product was purified using columnchromatography. Yield: 18.6 g (54%). ¹H-NMR (400 MHz, CDCl₃): δ 11.64(s, 1H, OH), 9.87 (s, 1H, CHO), 7.59 (d, J=2.4 Hz, 1H, Ar—H), 7.35 (d,J=2.4 Hz, 1H, Ar—H), 1.43 (s, 9H, t-Bu), 1.33 (s, 9H, t-Bu).

3-tert-Butyl-5-fluorosalicylaldehyde L^(2b)

2-tert-Butyl-4-fluorophenol L^(1b) was first prepared according to theliterature procedure described by DiCiccio et al. J. Am. Chem. Soc.2016. Next, L^(2b) was synthesized following the general proceduredetailed for Lea, expect that L^(1b) was used instead of L^(1a). Yield:43%. ¹H-NMR (400 MHz, CDCl₃): δ 11.59 (s, 1H, OH), 9.82 (s, 1H, —CHO),7.28 (dd, J=10.3, 2.9 Hz, 1H, Ar—H), 7.07 (dd, J=7.0, 3.1 Hz, 1H, Ar—H),1.41 (s, 9H, t-Bu).

3,5-Dicumylsalicylaldehyde L^(2c)

3,5-Dicumylsalicylaldehyde 2c was synthesized according to the generalprocedure detailed for L^(2a), except that 2,4-dicumylphenol L^(1c) wasused instead of 2,4-di-tert-butylphenol L^(1a). Yield: 57%. ¹H-NMR (400MHz, CDCl₃): δ 11.25 (s, 1H, OH), 9.77 (s, 1H, CHO), 7.51 (d, J=2.3 Hz,1H, Ar—H), 7.38-7.09 (m, 11H, Ar—H), 1.73 (s, 6H, Me), 1.64 (s, 6H, Me).

Synthesis of Salen Ligands L^(3a-c, and e) Salcy Ligand L^(3a)

A mixture of 3,5-bis(tert-butyl)salicylaldehyde Lea (7.03 g, 30 mmol)and racemic trans-1,2-diaminocyclohexane (1.71 g, 15.0 mmol) wasdissolved in methanol (80 mL), and about 0.2 mL formic acid was added tothe solution. The reaction was then heated to reflux for 6 h. Uponcooling, the yellow precipitate was collected by filtration and driedunder vacuum. Yield: 6.4 g (78%). ¹H-NMR (400 MHz, CDCl₃): δ 13.71 (s,2H, OH), 8.30 (s, 2H, N═CH), 7.28 (d, J=2.8 Hz, 2H, Ar—H), 6.98 (d,J=2.2 Hz, 2H, Ar—H), 3.32 (m, 2H, NCH), 1.94 (m, 2H, Cy-H), 1.86 (m, 2H,Cy-H), 1.75 (m, 2H, Cy-H), 1.47 (m, 2H, Cy-H), 1.41 (s, 9H, t-Bu), 1.23(s, 9H, t-Bu).

Salcy Ligand L^(3b)

L^(3b) was synthesized according to the general procedure detailed forL^(3a) expect that 3-tert-butyl-5-fluorosalicylaldehyde L^(2b) was usedinstead of 3,5-bis(tert-butyl)salicylaldehyde L^(2a). Yield: 75%. ¹H-NMR(400 MHz, CDCl₃): δ 13.57 (s, 2H, OH), 8.20 (s, 2H, N═CH), 6.99 (dd,J=10.7, 2.9 Hz, 2H, Ar—H), 6.67 (dd, J=7.8, 3.0 Hz, 2H, Ar—H), 3.39-3.24(m, 2H, NCH), 1.99 (m, 2H, Cy-H), 1.90 (m, 2H, Cy-H), 1.75 (m, 2H,Cy-H), 1.48 (m, 2H, Cy-H), 1.39 (s, 18H, t-Bu).

Salcy Ligand L^(3c)

L^(3c) was synthesized according to the general procedure detailed forL^(3a) expect that 3,5-dicumylsalicylaldehyde L^(2c) was used instead of3,5-bis(tert-butyl)salicylaldehyde L^(2a). Yield: 95%. ¹H-NMR (400 MHz,CDCl₃): δ 13.26 (s, 2H, OH), 8.10 (s, 2H, N═CH), 7.32-7.08 (m, 22H,Ar—H), 6.93 (s, 2H, Ar—H), 3.15 (m, 2H, NCH), 1.75 (m, 4H, Cy-H), 1.67(d, J=2.6 Hz, 12H, -Me), 1.65 (s, 6H, Me), 1.58 (s, 6H, Me), 1.57-1.48(m, 2H, Cy-H), 1.38-1.25 (m, 2H, Cy-H).

Salph Ligand L^(3e)

L^(3e) was synthesized according to the general procedure detailed forL^(3a) expect that 1,2-diaminobenzene was used instead of racemictrans-1,2-diaminocyclohexane. Yield: 85%. ¹H-NMR (400 MHz, CDCl₃): δ13.54 (s, 2H, OH), 8.66 (s, 2H, N═CH), 7.44 (d, J=2.4 Hz, 2H, Ar—H),7.34-7.29 (m, 2H, Ar—H), 7.25-7.20 (m, 4H, Ar—H), 1.43 (s, 18H), 1.32(s, 18H).

Synthesis of Yttrium Complexes Rac-4a-c, and e

Yttrium Complex 4a

Synthesis of yttrium complex 4a followed the literature proceduredescribed by Liu et al. Dalton Trans. 2008 with minor modificationsdetailed below. A solution of salcy ligand L^(3a) (0.547 g, 1.00 mmol)in hexanes (20 mL) was added to a solution of Y[N(SiHMe₂)₂]₃(THF)₂(0.630 g, 1.00 mmol) in hexanes (20 mL) and stirred for 24 h at roomtemperature. The volatiles were removed in vacuo, and the residue waswashed with cold hexanes. The product was obtained as pale yellow solid.Yield: 0.60 g (72%). ¹H-NMR (400 MHz, C₆D₆): δ 8.03 (s, 1H, Ar—H, N═CH),7.90 (s, 1H, N═CH), 7.73 (dd, J=8.9, 2.6 Hz, 2H, Ar—H), 7.32 (d, J=2.6Hz, 1H, Ar—H), 7.10 (d, J=2.5 Hz, 1H, Ar—H), 5.07 (dt, J=5.9, 2.8 Hz,2H, SiH—), 4.79 (m, 1H, NCH), 3.99 (m, 4H, THF), 2.29 (m, 1H, NCH), 1.76(s, 9H, t-Bu), 1.61 (s, 9H, t-Bu), 1.65-1.32 (m, 6H, Cy-H), 1.46 (m, 4H,THF), 1.40 (s, 9H, t-Bu), 1.37 (s, 9H, t-Bu), 1.04-0.82 (m, 2H, Cy-H),0.33 (dd, J=4.2, 3.2 Hz, 12H, SiMe). ¹³C-NMR (100 MHz, C₆D₆): δ 171.0,164.8, 164.0, 162.8, 139.5, 139.1, 136.8, 136.7, 130.3, 129.8, 129.7,129.6, 122.9, 122.6, 72.6, 70.3, 65.6, 35.9, 35.8, 34.2, 33.3, 31.9,31.8, 30.5, 30.2, 27.5, 25.7, 25.4, 25.1, 3.4, 3.1.

Yttrium Complex 4b

Yttrium complex 4b was synthesized according to the general proceduredetailed for 4a expect that salcy ligand L^(3b) was used instead ofL^(3a). The product was obtained as pale yellow solid. Yield: 73%.¹H-NMR (400 MHz, C₆D₆): δ 7.66 (s, 1H, N═CH), 7.50 (s, 1H, N═CH), 7.35(ddd, J=10.5, 3.3, 1.8 Hz, 2H, Ar—H), 6.81 (dd, J=8.2, 3.3 Hz, 1H,Ar—H), 6.64 (dd, J=8.4, 3.3 Hz, 1H, Ar—H), 5.01 (dt, J=6.0, 3.0 Hz, 2H,SiH—), 4.47 (m, 1H, NCH), 3.90 (m, 4H, THF), 2.18-2.02 (m, 1H, NCH),1.68-1.39 (m, 4H, Cy-H), 1.56 (s, 9H, t-Bu), 1.48 (s, 9H, t-Bu), 1.44(m, 4H, THF), 1.31-1.14 (m, 2H, Cy-H), 0.91-0.80 (m, 2H, Cy-H), 0.29(dd, J=3.0, 1.0 Hz, 12H, SiMe). ¹³C-NMR (100 MHz, C₆D₆): δ 169.6, 162.8,162.0, 161.8, 154.7, 152.4, 142.0, 141.7, 122.2, 120.6, 120.4, 120.2,117.3 (d, J=21.6 Hz), 116.9 (d, J=21.5 Hz), 71.9, 70.5, 65.8, 35.7,35.6, 33.1, 29.8, 29.6, 27.4, 25.5, 25.3, 24.9, 3.3, 3.0.

Yttrium Complex 4c

Yttrium complex 4c was synthesized according to the general proceduredetailed for 4a expect that salcy ligand L^(3c) was used instead ofL^(3a). The product was obtained as pale yellow solid. Yield: 83%.¹H-NMR (400 MHz, C₆D₆): δ 7.82 (s, 1H, N═CH), 7.70 (s, 1H, N═CH), 7.66(m, 2H, Ar—H), 7.50-7.40 (m, 4H, Ar—H), 7.40-7.34 (m, 4H, Ar—H),7.28-7.18 (m, 9H, Ar—H), 7.15-7.02 (m, 5H, Ar—H), 4.61 (m, 2H, SiH—),4.38 (m, 1H, NCH), 3.36 (s, 4H, THF), 2.12 (m, 1H, NCH), 2.10 (s, 3H,Me), 1.95 (s, 3H, Me), 1.80 (s, 3H, Me), 1.72 (d, J=2.4 Hz, 6H, Me),1.70 (s, 6H, Me), 1.66 (s, 3H, Me), 1.59-1.19 (m, 10H, Cy-H, THF),0.84-0.57 (m, 2H, Cy-H), 0.10 (m, 12H, SiMe). ¹³C-NMR (100 MHz, C₆D₆): δ170.5, 164.6, 164.0, 162.6, 152.1, 151.6, 151.5, 151.4, 138.5, 138.0,136.6, 136.4, 133.0, 132.9, 132.7, 132.2, 128.4, 128.3, 128.2, 127.2,126.7, 126.6, 126.0, 125.5, 125.3, 123.2, 122.8, 72.1, 69.4, 65.4, 43.4,43.4, 42.6, 33.6, 33.2, 33.0, 31.4, 31.3, 28.6, 27.7, 27.3, 25.9, 25.6,24.9, 3.2, 2.9.

Yttrium Complex 4e

Yttrium complex 4e was synthesized according to the general proceduredetailed for 4a expect that salph ligand L^(3e) was used instead ofL^(3a) (Scheme 9). The product was obtained as yellow solid. Yield: 58%.¹H-NMR (400 MHz, C₆D₆): δ 8.25 (s, 2H, N═CH), 7.77 (d, J=2.5 Hz, 2H,Ar—H), 7.21 (d, J=2.5 Hz, 2H, Ar—H), 7.08-6.96 (m, 4H, Ar—H), 4.81 (dt,J=5.7, 2.8 Hz, 2H, SiH—), 4.17 (m, 4H, THF), 1.69 (s, 18H, t-Bu),1.55-1.45 (m, 4H, THF), 1.39 (s, 18H, t-Bu), 0.07 (d, J=3.0 Hz, 12H,SiMe₃). ¹³C-NMR (100 MHz, C₆D₆): δ 166.5, 165.8, 146.2, 139.8, 137.3,130.8, 130.6, 127.5, 122.7, 118.8, 70.8, 35.9, 34.2, 31.8, 30.4, 25.4,3.1.

Example 3. Synthesis of Yttrium Complex 4d

The following illustrates a process for preparing a racemic yttriumcomplex 4d.

3-Trityl-5-methylsalicylaldehyde L^(2d)

2-Trityl-4-methylphenol L^(1d) was prepared first according to theliterature procedure described by Kochnev et al. Russ. Chem. Bull. Int.Ed. 2008. Next, a mixture of L^(1d) (5.26 g, 15 mmol),hexamethylenetetraine (4.2 g, 30 mmol), and CF₃COOH (15 mL) was heatedfor 4 h at 115-125° C., and then cooled down to 75-80° C. H₂SO₄ (33%aq., 23 mL) was added to the reaction, and the resulting mixture washeated for 1-2 h at 125-130° C. After cooling down to room temperature,ethyl acetate (40 mL) and water (50 mL) were added. The organic layerwas separated and water was extracted with ethyl acetate (3×20 mL). Thecombined extracts were washed with water (70 mL) and brine (50 mL),separated, and dried over anhydrous Na₂SO₄. The product was purified bycolumn chromatography. Yield: 4.50 g (79%).

Salcy Ligand L^(3d)

According to the literature procedure described by Char et al. C. R.Chimie. 2016, a mixture of racemic trans-1,2-diaminocyclohexane (0.34 g,3 mmol) and 3-trityl-5-methylsalicylaldehyde L^(2d) (2.28 g, 6 mmol) in30 mL of dichloromethane was stirred under reflux overnight. Allvolatiles were removed via rotary evaporator. The product (L³d) was thenwas purified by recrystallization from ethanol. Yield: 2.38 g (95%).¹H-NMR (400 MHz, CDCl₃): δ 13.20 (s, 2H, OH), 7.96 (s, 2H, N═CH),7.21-7.12 (m, 30H, Ar—H), 7.04 (s, 2H, Ar—H), 6.95 (m, 2H, Ar—H), 3.10(m, 2H, NCH), 2.24 (s, 6H, Me), 1.73 (m, 4H, Cy-H), 1.55 (m, 2H, Cy-H),1.27 (m, 2H, Cy-H).

Yttrium Complex 4d

A solution of salen ligand Lad (0.585 g, 0.70 mmol) in toluene (15 mL)was added to a solution of Y[N(SiHMe₂)₂]₃(THF)₂ (0.441 g, 0.70 mmol) intoluene (15 mL) and stirred for 24 h at room temperature. The volatileswere removed in vacuo, and the residue was washed with cold hexanes. Theproduct was obtained as yellow solid. Yield: 0.602 g (82%). Anal. Calc.for C₆₄H₆₆N₃O₂Si₂Y: C, 72.9; H, 6.3; N, 4.0. Found: C, 72.9; H, 6.6; N,3.7%.

¹H-NMR (400 MHz, C₆D₆): δ 7.83 (s, 1H, N═CH), 7.68 (s, 1H, N═CH), 7.58(dd, J=5.2, 2.2 Hz, 2H, Ar—H), 7.50 (m, 6H, Ar—H), 7.42 (m, 6H, Ar—H),7.13-6.96 (m, 19H, Ar—H), 6.82 (d, J=1.9 Hz, 1H, Ar—H), 4.39 (dt, J=5.9,2.9 Hz, 2H, SiH—), 3.97 (m, 1H, NCH), 2.14-2.10 (m, 1H, NCH), 2.10 (s,3H, Me), 2.06 (s, 3H, Me), 1.90-1.71 (m, 2H, Cy-H), 1.61-1.42 (m, 2H,Cy-H), 1.23-0.99 (m, 2H, Cy-H), 0.91-0.67 (m, 2H, Cy-H), 0.15 (d, J=3.0Hz, 6H, SiMe), 0.01 (d, J=2.9 Hz, 6H, SiMe). ¹³C-NMR (100 MHz, C₆D₆): δ168.7, 164.0, 163.3, 163.1, 147.2, 139.5, 138.1, 136.7, 135.3, 131.9,131.8, 127.6, 127.6, 126.0, 125.7, 124.4, 124.2, 123.5, 123.4, 69.4,64.9, 64.5, 64.4, 31.6, 28.2, 25.2, 24.6, 20.7, 3.4, 3.0.

Example 4. Synthesis of Enantiomeric Yttrium Complexes (R,R)-4d and(S,S)-4d

Synthesis of Enantiopure Salcy Ligand L^(3d) Salcy Ligand (R,R)-L^(3d)

A mixture of (1R,2R)-(−)-1,2-diaminocyclohexane (0.34 g, 3 mmol) and3-trityl-5-methylsalicylaldehyde L^(2d) (2.28 g, 6 mmol) in 30 mL ofdichloromethane was stirred under reflux overnight. All volatiles wereremoved via rotary evaporator. The product [(R,R)-L^(3d)] was thenpurified by recrystallization from ethanol; yield: 2.33 g (93%). ¹H-NMR(400 MHz, CDCl₃): δ 13.14 (s, 2H, OH), 7.88 (s, 2H, N═CH), 7.22-7.08 (m,30H, Ar—H), 7.03 (d, J=2.0 Hz, 2H, Ar—H), 6.81 (d, J=1.7 Hz, 2H, Ar—H),3.08-2.89 (m 2H, NCH), 2.24 (s, 6H, Me), 1.80-1.66 (m, 4H, Cy-H),1.57-1.41 (m, 2H, Cy-H), 1.35-1.17 (m, 2H, Cy-H). [α]_(D) ²³=−334.4°(c=0.519 g/100 mL, chloroform).

Salcy Ligand (S,S)-L^(3d)

A mixture of (1S,2S)-(+)-1,2-diaminocyclohexane (0.34 g, 3 mmol) and3-trityl-5-methylsalicylaldehyde L^(2d) (2.28 g, 6 mmol) in 30 mL ofdichloromethane was stirred under reflux overnight. All volatiles wereremoved via rotary evaporator. The product [(S,S)-L^(3d)] was thenpurified by recrystallization from ethanol; yield: 2.31 g (92%). ¹H-NMR(400 MHz, CDCl₃): δ 13.14 (s, 2H, OH), 7.88 (s, 2H, N═CH), 7.21-7.09 (m,30H, Ar—H), 7.03 (d, J=1.9 Hz, 2H, Ar—H), 6.81 (d, J=1.7 Hz, 2H, Ar—H),3.07-2.91 (m 2H, NCH), 2.24 (s, 6H, Me), 1.81-1.66 (m, 4H, Cy-H),1.59-1.40 (m, 2H, Cy-H), 1.37-1.19 (m, 2H, Cy-H). [α]_(D) ²³=+336.8(c=0.366 g/100 mL, chloroform).

Synthesis of Enantiomeric Yttrium Complexes (R,R)-4d and (S,S)-4dYttrium Complex (R,R)-4d

A solution of salcy ligand (R,R)-L^(3d) (0.668 g, 0.80 mmol) in toluene(15 mL) was added to a solution of Y[N(SiHMe₂)₂]₃(THF)₂ (0.504 g, 0.80mmol) in toluene (15 mL) and stirred for 3 days at room temperature. Thevolatiles were removed in vacuo, and the residue was washed with coldhexanes. The product was obtained as yellow solid; yield: 0.680 g (81%).¹H-NMR (400 MHz, C₆D₆): δ 7.83 (s, 1H, N═CH), 7.68 (s, 1H, N═CH), 7.58(dd, J=5.3, 2.3 Hz, 2H, Ar—H), 7.53-7.46 (m, 6H, Ar—H), 7.45-7.37 (m,6H, Ar—H), 7.13-6.95 (m, 19H, Ar—H), 6.82 (d, J=2.1 Hz, 1H, Ar—H), 4.39(dt, J=5.9, 2.9 Hz, 2H, SiH—), 3.97 (m, 1H, NCH), 2.10 (s, 3H, Me), 2.06(s, 3H, Me), 1.92-1.69 (m, 3H, Cy-H), 1.62-1.41 (m, 2H, Cy-H), 1.23-0.99(m, 2H, Cy-H), 0.91-0.68 (m, 2H, Cy-H), 0.15 (d, J=3.0 Hz, 6H, SiMe₂),0.01 (d, J=3.0 Hz, 6H, SiMe₂). ¹³C-NMR (101 MHz, C₆D₆): δ 168.7, 164.0,163.3, 163.1, 147.2, 139.5, 138.1, 136.7, 135.3, 131.9, 131.8, 127.7,127.6, 126.0, 125.7, 124.4, 124.2, 123.5, 123.4, 69.4, 64.9, 64.5, 64.4,31.6, 28.2, 25.2, 24.6, 20.7, 3.4, 3.0. [α]_(D) ²³=−376.4° (c=0.426g/100 mL, toluene).

Yttrium Complex (S,S)-4d

A solution of salcy ligand (S,S)-L^(3d) (0.668 g, 0.80 mmol) in toluene(15 mL) was added to a solution of Y[N(SiHMe₂)₂]₃(THF)₂ (0.504 g, 0.80mmol) in toluene (15 mL) and stirred for 3 days at room temperature. Thevolatiles were removed in vacuo, and the residue was washed with coldhexanes. The product was obtained as yellow solid; yield: 0.710 g (84%).¹H-NMR (400 MHz, C₆D₆): δ 7.83 (s, 1H, N═CH), 7.68 (s, 1H, N═CH), 7.58(dd, J=5.3, 2.2 Hz, 2H, Ar—H), 7.53-7.45 (m, 6H, Ar—H), 7.45-7.38 (m,6H, Ar—H), 7.14-6.95 (m, 19H, Ar—H), 6.82 (d, J=1.9 Hz, 1H, Ar—H), 4.39(dt, J=5.8, 2.8 Hz, 2H, SiH—), 3.97 (t, J=10.7 Hz, 1H, NCH), 2.10 (s,3H, Me), 2.06 (s, 3H, Me), 1.93-1.71 (m, 3H, Cy-H), 1.63-1.42 (m, 2H,Cy-H), 1.29-1.01 (m, 2H, Cy-H), 0.93-0.71 (m, 2H, Cy-H), 0.15 (d, J=3.0Hz, 6H, SiMe₂), 0.01 (d, J=2.9 Hz, 6H, SiMe₂). ¹³C-NMR (101 MHz, c₆d₆) δ168.7, 164.0, 163.3, 163.1, 147.2, 139.5, 138.1, 136.7, 135.3, 131.9,131.8, 127.7, 127.6, 126.0, 125.7, 124.4, 124.2, 123.6, 123.4, 69.4,64.9, 64.5, 64.4, 31.6, 28.2, 25.2, 24.6, 20.7, 3.4, 3.0. [α]_(D)²³=+384.8 (c=0.442 g/100 mL, toluene).

Example 5. Procedures for Kinetic Resolution of Rac-DL by Enantiomeric YComplexes (R,R)-4d and (S,S)-4d

Polymerizations were performed in 5.5 mL glass reactors inside the inertglovebox at room temperature. The reactor was charged with apredetermined amount of catalyst and/or initiator and solvent (asspecified in the polymerization tables) in a glovebox. The mixture wasstirred at room temperature for 10 min, and the polymerization wasinitiated by rapid addition of rac-DL solution. After a desired timeperiod, the polymerization was immediately quenched by addition of 0.5mL of benzoic acid/chloroform (10 mg/mL) and a 0.02 mL of aliquot wastaken from the reaction mixture and prepared for ¹H-NMR analysis toobtain the percent monomer conversion data. The quenched mixture wasthen precipitated into 50 mL of cold methanol while stirring, filtered,washed with cold methanol to remove any unreacted monomer, and dried ina vacuum oven at room temperature overnight to a constant weight.

Rac-DL was polymerized by (R,R)-4d or (S,S)-4d according to the abovegeneral procedure. The conversion of monomer was ˜50% with the[rac-DL]/[(R,R)-4d] molar ration of 400 or 800 after 20 min, under whichcondition the conversion was 100% with rac-4d as the catalyst. Thepolymerization was then quenched with benzoic acid/DCM (caution: avoidusing nucleophiles such as methanol or acidified methanol as they reactwith the unreacted monomer, see Scheme 13). The solvent was evaporated,and the solid residue was sublimated at 40-50° C. under vacuum torecover the pure unreacted monomer. The residue in the sublimator wasdissolved in about 2 mL DCM, precipitated into 60 mL MeOH, filtrated,washed, and dried in vacuum to recover the polymer. The recoveredunreacted monomer was analyzed by a chiral HPLC system to measure e.e.values, and the stereosectivity factors was calculated from eq. 1:

$\begin{matrix}{{s = \frac{\ln\left\lbrack {\left( {1 - c} \right)\left( {1 - {ee}_{m}} \right)} \right\rbrack}{\ln\left\lbrack {\left( {1 - c} \right)\left( {1 + {ee}_{m}} \right)} \right\rbrack}},} & \left( {{{eq}.\mspace{14mu} S}\; 1} \right) \\{{{{Where}\mspace{14mu} c} = {1 - \frac{\lbrack S\rbrack + \lbrack R\rbrack}{\lbrack S\rbrack_{0} + \lbrack R\rbrack_{0}}}},{{ee}_{m} = {\frac{\lbrack S\rbrack - \lbrack R\rbrack}{\lbrack S\rbrack + \lbrack R\rbrack}.}}} & \left( {{eq}.\mspace{14mu} 1} \right)\end{matrix}$

Example 6. Preparation of a Highly Isotactic Polymer

Polymerizations were performed in 5.5 mL glass reactors inside the inertglovebox at room temperature. The reactor was charged with apredetermined amount of catalyst and/or initiator and solvent (asspecified in the polymerization tables) in a glovebox. The mixture wasstirred at room temperature for 10 min, and the polymerization wasinitiated by rapid addition of rac-DL solution. After a desired timeperiod, the polymerization was immediately quenched by addition of 0.5mL of benzoic acid/chloroform (10 mg/mL) and a 0.02 mL of aliquot wastaken from the reaction mixture and prepared for ¹H NMR analysis toobtain the percent monomer conversion data. The quenched mixture wasthen precipitated into 50 mL of cold methanol while stirring, filtered,washed with cold methanol to remove any unreacted monomer, and dried ina vacuum oven at room temperature overnight to a constant weight.

Example 7. ROP of Rac-DL_(Et)

The ethyl derivative, rac-eight-membered cyclic diolide (rac-DL_(Et)),was prepared according to the procedures already described for themethyl derivative, rac-eight-membered cyclic diolide (rac-DL), exceptthat ethyl iodide was used to replace methyl iodide.

The ring-opening polymerization of rac-DL_(Et) was performed in 5.5 mLglass reactors inside the inert glovebox at room temperature. Thereactor was charged with roc-DL_(Et) (160 mg, 0.8 mmol) anddichloromethane (DCM, 0.5 mL) in a glovebox, and the polymerization wasstarted by rapid addition of the mixture of catalyst 4c (4.35 mg, 4μmol) and BnOH (0.43 mg, 4 μmol) as an initiator in DCM (0.3 mL). After60 min, the polymerization was immediately quenched by addition of 0.5mL of benzoic acid/chloroform (10 mg/mL) and a 0.05 mL of aliquot wastaken from the reaction mixture and prepared for ¹H-NMR analysis toobtain the percent monomer conversion data (100%). The quenched mixturewas then precipitated into 50 mL of cold methanol while stirring,filtered, washed with cold methanol, and dried in a vacuum oven at roomtemperature overnight to a constant weight (145 mg). The resultingpolymer, poly(3-hydroxyvalerate) or P3HV (M_(n)=48.7 kg/mol, Ð=1.23)showed a P_(m) of 0.96 and isotactic [mm] triad of 95%. The T_(g)=−17.4°C., T_(c)=62.6° C., and T_(m)=108° C. were observed on the DSC curvewith the heating and cooling rate of 2° C./min, while it exhibited adecomposition temperature (T_(d)) (defined by the temperature of 5%weight loss in the TGA curve) of 258° C. and a maximum ratedecomposition temperature (T_(max)) of 285° C.

¹H-NMR (400 MHz, CDCl₃): δ 5.13-5.03 (m, 2H, EtCHO—C═O), v_(A)=2.68,v_(B)=2.51, (AB of ABX, J_(AB)=11.3, J_(AX)=10.2, J_(BX)=3.5, 4H,C(═O)CH₂), 1.86-1.63 (m, 4H, CH₂CH₃), 1.01 (t, J=7.4 Hz, 6H, Me).

Example 8. Copolymerization of Rac-DL and Rac-DL_(Et)

Copolymerization of rac-DL and rac-DL_(Et) with an appropriate catalystprovides the corresponding poly(3-hydroxybutyrate-co-3-hydroxyvalerate),as shown in Scheme 16, which is an example of a copolymer of Formula II.

The copolymerization of rac-DL and rac-DL_(Et) was performed in 5.5 mLglass reactors inside the inert glovebox at room temperature. Thereactor was charged with rac-DL (103.3 mg, 0.6 mmol), rac-DL_(Et) (40.0mg, 0.2 mmol) and DCM (0.5 mL) in a glovebox, and the polymerization wasstarted by rapid addition of the mixture of catalyst 4c (2.17 mg, 2μmol) and BnOH (0.22 mg, 2 μmol) as an initiator in DCM (0.3 mL). After30 min, the polymerization was immediately quenched by addition of 0.5mL of benzoic acid/chloroform (10 mg/mL) and a 0.05 mL of aliquot wastaken from the reaction mixture and prepared for ¹H-NMR analysis toobtain the percent monomer conversion data (rac-DL: 95%; rac-DL_(Et):53%). The quenched mixture was then precipitated into 50 mL of coldmethanol while stirring, filtered, washed with cold methanol, and driedin a vacuum oven at room temperature overnight to a constant weight (103mg). The resulting copolymer PHBV (M_(n)=76.6 kg/mol, Ð=1.18, P3HV%=15.7%) showed a T_(g)=0.4° C., T_(c)=82.2° C., and T_(m)=138° C. onthe DSC curve with the heating and cooling rate of 5° C./min, while itexhibited a T_(d) of 258° C. and a T_(max) of 286° C.

Example 9. ROP of Meso-DL

The following illustrates a process for preparing a highly syndiotacticpolymer from the ring opening polymerization of meso-DL to provide apolymer of Formula I.

The ring-opening polymerization of meso-DL was performed in 5.5 mL glassreactors inside the inert glovebox at room temperature. The reactor wascharged with meso-DL (138 mg, 0.8 mmol) and THF (0.5 mL) in a glovebox,and the polymerization was started by rapid addition of the mixture ofcatalyst (R,R)-4d (8.43 mg, 8 μmol) and BnOH (0.86 mg, 8 μmol) as aninitiator in THF (0.3 mL). After 10 h, the polymerization wasimmediately quenched by addition of 0.5 mL of benzoic acid/chloroform(10 mg/mL) and a 0.05 mL of aliquot was taken from the reaction mixtureand prepared for ¹H-NMR analysis to obtain the percent monomerconversion datum (97%). The quenched mixture was then precipitated into50 mL of cold methanol while stirring, filtered, washed with coldmethanol, and dried in a vacuum oven at room temperature overnight to aconstant weight (125 mg). The resulting syndiotactic P3HB (M_(n)=31.6kg/mol, Ð=1.16) showed a P_(r) of ˜0.95. The T_(c)=145.4° C., andT_(m)=175.8° C. were observed on DSC curve with the heating and coolingrate of 10° C./min, while it exhibited a T_(d) 247° C. and a T_(max) of275° C.

Example 10. Copolymerization of Rac-DL and Meso-DL

The following illustrates a process for preparing a copolymer of rac-DLand meso-DL to provide a polymer of Formula II.

The copolymerization of rac-DL and meso-DL was performed in 5.5 mL glassreactors inside the inert glovebox at room temperature. The reactor wascharged with rac-DL (69 mg, 0.4 mmol), meso-DL (69 mg, 0.4 mmol) and DCM(0.5 mL) in a glovebox, and the polymerization was started by rapidaddition of the mixture of catalyst rac-4d (8.43 mg, 8 μmol) and BnOH(0.86 mg, 8 μmol) as an initiator in DCM (0.3 mL). After 35 min, thepolymerization was immediately quenched by addition of 0.5 mL of benzoicacid/chloroform (10 mg/mL) and a 0.05 mL of aliquot was taken from thereaction mixture and prepared for ¹H-NMR analysis to obtain the percentmonomer conversion data (rac-DL: 100%; meso-DL: 100%). The quenchedmixture was then precipitated into 50 mL of cold methanol whilestirring, filtered, washed with cold methanol, and dried in a vacuumoven at room temperature overnight to a constant weight (129 mg). Theresulting tapered isotactic-b-syndiotactic block P3HB (M_(n)=22.2kg/mol, Ð=1.01) showed a T_(g)=1.3° C., and two T_(c)'s (68.7 and 86.7°C.), and two T_(m)'s (115.0 and 135.0° C.) on the DSC curve with theheating and cooling rate of 2° C./min, while it exhibited a T_(d) 252°C. and a T_(max) of 278° C.

Example 11. Copolymerization of Rac-DL and ε-CL

The following illustrates a process for preparing a copolymer of rac-DLand ε-CL to provide a polymer of Formula IV.

The copolymerization of rac-DL and ε-CL was performed in 5.5 mL glassreactors inside the inert glovebox at room temperature. The reactor wascharged with rac-DL (138 mg, 0.8 mmol), ε-CL (91 mg, 0.8 mmol) and DCM(0.7 mL) in a glovebox, and the polymerization was started by rapidaddition of the mixture of catalyst rac-4d (8.43 mg, 8 μmol) and BnOH(0.86 mg, 8 μmol) as an initiator in DCM (0.3 mL). After 25 min, thepolymerization was immediately quenched by addition of 0.5 mL of benzoicacid/chloroform (10 mg/mL) and a 0.05 mL of aliquot was taken from thereaction mixture and prepared for ¹H-NMR analysis to obtain the percentmonomer conversion data (rac-DL: 100%; ε-CL: 100%). The quenched mixturewas then precipitated into 80 mL of cold methanol while stirring,filtered, washed with cold methanol, and dried in a vacuum oven at roomtemperature overnight to a constant weight (198 mg). The resultingblocked copolymer P3HB-b-PCL (M_(n)=47.2 kg/mol, Ð=1.14) showed twoT_(c)'s (10.9 and 55.5° C.), and two T_(m)'s (54.2 and 161.2° C.) on DSCcurve with the heating and cooling rate of 5° C./min, while it exhibitedtwo onset degradation temperatures (T_(d)) (determined by the point ofintersection of tangents to two branches of the thermogravimetric curve)of 256 and 374° C. and two maximum rate decomposition temperatures(T_(max)) of 279 and 403° C.

While specific embodiments have been described above with reference tothe disclosed embodiments and examples, such embodiments are onlyillustrative and do not limit the scope of the invention. Changes andmodifications can be made in accordance with ordinary skill in the artwithout departing from the invention in its broader aspects as definedin the following claims.

All publications, patents, and patent documents are incorporated byreference herein, as though individually incorporated by reference. Nolimitations inconsistent with this disclosure are to be understoodtherefrom. The invention has been described with reference to variousspecific and preferred embodiments and techniques. However, it should beunderstood that many variations and modifications may be made whileremaining within the spirit and scope of the invention.

What is claimed is:
 1. A highly isotactic polymer comprising Formula I:

wherein: n is about 10 to about 10,000; R is (C₁-C₁₈)alkyl,(C₁-C₈)alkenyl, (C₁-C₈)alkynyl, benzyl, or aryl; and Formula I comprisesat least 95% isotactic triads with respect to the stereocenters ofsubstituents R on the polymer chain, wherein the at least 95% isotactictriads (mm) have consecutive (R) stereochemical configurations orconsecutive (S) stereochemical configurations.
 2. The polymer of claim 1wherein the polymer comprises at least 99% isotactic triads with respectto the stereocenters of substituents R on polymer chain.
 3. The polymerof claim 2 wherein the molecular weight M_(n) is at least about 100 kDa.4. The polymer of claim 1 wherein the polymer has a melting temperature,T_(m)of at least 170° C.
 5. A composition comprising polymers of claim 1wherein the composition comprises approximately equal amounts ofpolymers having isotactic triads of (R) stereochemical configurationsand polymers having isotactic triads of (S) stereochemicalconfigurations.
 6. The composition of claim 5 wherein the dispersityindex M_(w)/M_(n) of the polymers is less than 1.2.
 7. A copolymercomprising a polymer of claim 1 and a polyester of lactone monomers.